{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:51:14Z","timestamp":1794009074980,"version":"4.8.0"},"reference-count":232,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T00:00:00Z","timestamp":1675900800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T00:00:00Z","timestamp":1675900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"University of Eastern Finland (UEF) including Kuopio University Hospital"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mol Med"],"published-print":{"date-parts":[[2023,3]]},"abstract":"\n Abstract<\/jats:title>\n \n Gut microbiota in interaction with intestinal host tissues influences many brain functions and microbial dysbiosis has been linked with brain disorders, such as neuropsychiatric conditions and Alzheimer\u2019s disease (AD).\n l<\/jats:sc>\n -tryptophan metabolites and short-chained fatty acids (SCFA) are major messengers in the microbiota-brain axis. Aryl hydrocarbon receptors (AhR) are main targets of tryptophan metabolites in brain microvessels which possess an enriched expression of AhR protein. The Ah receptor is an evolutionarily conserved, ligand-activated transcription factor which is not only a sensor of xenobiotic toxins but also a pleiotropic regulator of both developmental processes and age-related tissue degeneration. Major microbiota-produced tryptophan metabolites involve indole derivatives, e.g., indole 3-pyruvic acid, indole 3-acetaldehyde, and indoxyl sulfate, whereas indoleamine and tryptophan 2,3-dioxygenases (IDO\/TDO) of intestine host cells activate the kynurenine (KYN) pathway generating KYN metabolites, many of which are activators of AhR signaling. Chronic kidney disease (CKD) increases the serum level of indoxyl sulfate which promotes AD pathogenesis, e.g., it disrupts integrity of blood\u2013brain barrier (BBB) and impairs cognitive functions. Activation of AhR signaling disturbs vascular homeostasis in brain; (i) it controls blood flow via the renin-angiotensin system, (ii) it inactivates endothelial nitric oxide synthase (eNOS), thus impairing NO production and vasodilatation, and (iii) it induces oxidative stress, stimulates inflammation, promotes cellular senescence, and enhances calcification of vascular walls. All these alterations are evident in cerebral amyloid angiopathy (CAA) in AD pathology. Moreover, AhR signaling can disturb circadian regulation and probably affect glymphatic flow. It seems plausible that dysbiosis of gut microbiota impairs the integrity of BBB via the activation of AhR signaling and thus aggravates AD pathology.\n <\/jats:p>\n <\/jats:sec>\n \n Key messages<\/jats:title>\n \n \n \n Dysbiosis of gut microbiota is associated with dementia and Alzheimer\u2019s disease.<\/jats:p>\n <\/jats:list-item>\n \n Tryptophan metabolites are major messengers from the gut host-microbiota to brain.<\/jats:p>\n <\/jats:list-item>\n \n Tryptophan metabolites activate aryl hydrocarbon receptor (AhR) signaling in brain.<\/jats:p>\n <\/jats:list-item>\n \n The expression of AhR protein is enriched in brain microvessels and blood-brain barrier.<\/jats:p>\n <\/jats:list-item>\n \n Tryptophan metabolites disturb brain vascular integrity via AhR signaling.<\/jats:p>\n <\/jats:list-item>\n \n Dysbiosis of gut microbiota promotes inflammation and AD pathology via AhR signaling.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1007\/s00109-023-02289-5","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T15:36:57Z","timestamp":1675957017000},"page":"201-222","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":152,"title":["Activation of aryl hydrocarbon receptor (AhR) in Alzheimer\u2019s disease: role of tryptophan metabolites generated by gut host-microbiota"],"prefix":"10.1007","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6691-6909","authenticated-orcid":false,"given":"Antero","family":"Salminen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,2,9]]},"reference":[{"key":"2289_CR1","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1146\/annurev-genom-090711-163814","volume":"13","author":"EA Grice","year":"2012","unstructured":"Grice EA, Segre JA (2012) The human microbiome: our second genome. Annu Rev Genomics Hum Genet 13:151\u2013170. https:\/\/doi.org\/10.1146\/annurev-genom-090711-163814","journal-title":"Annu Rev Genomics Hum Genet"},{"key":"2289_CR2","doi-asserted-by":"publisher","unstructured":"Li C, Liang Y, Qiao Y (2022) Messengers from the gut: gut microbiota-derived metabolites on host regulation. Front Microbiol 13:863407. https:\/\/doi.org\/10.3389\/fmicb.2022.863407","DOI":"10.3389\/fmicb.2022.863407"},{"key":"2289_CR3","doi-asserted-by":"publisher","unstructured":"Doifode T, Giridharan VV, Generoso JS, Bhatti G, Collodel A, Schulz PE, Forlenza OV, Barichello T (2021) The impact of the microbiota-gut-brain axis on Alzheimer\u2019s disease pathophysiology. Pharmacol Res 164:105314. https:\/\/doi.org\/10.1016\/j.phrs.2020.105314","DOI":"10.1016\/j.phrs.2020.105314"},{"key":"2289_CR4","doi-asserted-by":"publisher","first-page":"361","DOI":"10.3390\/nu13020361","volume":"13","author":"F Leblhuber","year":"2021","unstructured":"Leblhuber F, Ehrlich D, Steiner K, Geisler S, Fuchs D, Lanser L, Kurz K (2021) The immunopathogenesis of Alzheimer\u2019s disease is related to the composition of gut microbiota. Nutrients 13:361. https:\/\/doi.org\/10.3390\/nu13020361","journal-title":"Nutrients"},{"key":"2289_CR5","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s13024-022-00522-2","volume":"17","author":"D Bairamian","year":"2022","unstructured":"Bairamian D, Sha S, Rolhion N, Sokol H, Dorothee G, Lemere CA, Krantic S (2022) Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer\u2019s disease. Mol Neurodegener 17:19. https:\/\/doi.org\/10.1186\/s13024-022-00522-2","journal-title":"Mol Neurodegener"},{"key":"2289_CR6","doi-asserted-by":"publisher","first-page":"1859812","DOI":"10.1080\/19490976.2020.1859812","volume":"12","author":"F Dong","year":"2020","unstructured":"Dong F, Perdew GH (2020) The aryl hydrocarbon receptor as a mediator of host-microbiota interplay. Gut Microbes 12:1859812. https:\/\/doi.org\/10.1080\/19490976.2020.1859812","journal-title":"Gut Microbes"},{"key":"2289_CR7","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1080\/19490976.2020.1758008","volume":"11","author":"N Ma","year":"2020","unstructured":"Ma N, He T, Johnston LJ, Ma X (2020) Host-microbiome interactions: the aryl hydrocarbon receptor as a critical node in tryptophan metabolites to brain signaling. Gut Microbes 11:1203\u20131219. https:\/\/doi.org\/10.1080\/19490976.2020.1758008","journal-title":"Gut Microbes"},{"key":"2289_CR8","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s00109-016-1486-0","volume":"95","author":"HU Lee","year":"2017","unstructured":"Lee HU, McPherson ZE, Tan B, Korecka A, Pettersson S (2017) Host-microbiome interactions: the aryl hydrocarbon receptor and the central nervous system. J Mol Med (Berl) 95:29\u201339. https:\/\/doi.org\/10.1007\/s00109-016-1486-0","journal-title":"J Mol Med (Berl)"},{"key":"2289_CR9","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1007\/s00018-022-04520-x","volume":"79","author":"A Salminen","year":"2022","unstructured":"Salminen A (2022) Aryl hydrocarbon receptor (AhR) reveals evidence of antagonistic pleiotropy in the regulation of the aging process. Cell Mol Life Sci 79:489. https:\/\/doi.org\/10.1007\/s00018-022-04520-x","journal-title":"Cell Mol Life Sci"},{"key":"2289_CR10","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.3390\/ijms21061983","volume":"21","author":"NA Ramos-Garcia","year":"2020","unstructured":"Ramos-Garcia NA, Orozco-Ibarra M, Estudillo E, Elizondo G, Gomez Apo E, Chavez Macias LG, Sosa-Ortiz AL, Torres-Ramos MA (2020) Aryl hydrocarbon receptor in post-mortem hippocampus and in serum from young, elder, and Alzheimer\u2019s patients. Int J Mol Sci 21:1983. https:\/\/doi.org\/10.3390\/ijms21061983","journal-title":"Int J Mol Sci"},{"key":"2289_CR11","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.1253\/circj.cj-14-0343","volume":"78","author":"L Xiao","year":"2014","unstructured":"Xiao L, Zhang Z, Luo X (2014) Roles of xenobiotic receptors in vascular pathophysiology. Circ J 78:1520\u20131530. https:\/\/doi.org\/10.1253\/circj.cj-14-0343","journal-title":"Circ J"},{"key":"2289_CR12","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/nrn3114","volume":"12","author":"BV Zlokovic","year":"2011","unstructured":"Zlokovic BV (2011) Neurovascular pathways to neurodegeneration in Alzheimer\u2019s disease and other disorders. Nat Rev Neurosci 12:723\u2013738. https:\/\/doi.org\/10.1038\/nrn3114","journal-title":"Nat Rev Neurosci"},{"key":"2289_CR13","doi-asserted-by":"publisher","unstructured":"Huang Z, Wong LW, Su Y, Huang X, Wang N, Chen H, Yi C (2020) Blood-brain barrier integrity in the pathogenesis of Alzheimer\u2019s disease. Front Neuroendocrinol 59:100857. https:\/\/doi.org\/10.1016\/j.yfrne.2020.100857","DOI":"10.1016\/j.yfrne.2020.100857"},{"key":"2289_CR14","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.cotox.2017.02.003","volume":"2","author":"ME Hahn","year":"2017","unstructured":"Hahn ME, Karchner SI, Merson RR (2017) Diversity as opportunity: insights from 600 million years of AHR evolution. Curr Opin Toxicol 2:58\u201371. https:\/\/doi.org\/10.1016\/j.cotox.2017.02.003","journal-title":"Curr Opin Toxicol"},{"key":"2289_CR15","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.plipres.2017.06.001","volume":"67","author":"DW Nebert","year":"2017","unstructured":"Nebert DW (2017) Aryl hydrocarbon receptor (AHR): \u201cpioneer member\u201d of the basic-helix\/loop\/helix per-Arnt-sim (bHLH\/PAS) family of \u201csensors\u201d of foreign and endogenous signals. Prog Lipid Res 67:38\u201357. https:\/\/doi.org\/10.1016\/j.plipres.2017.06.001","journal-title":"Prog Lipid Res"},{"key":"2289_CR16","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1039\/c6fo01810f","volume":"8","author":"Z Xue","year":"2017","unstructured":"Xue Z, Li D, Yu W, Zhang Q, Hou X, He Y, Kou X (2017) Mechanisms and therapeutic prospects of polyphenols as modulators of the aryl hydrocarbon receptor. Food Funct 8:1414\u20131437. https:\/\/doi.org\/10.1039\/c6fo01810f","journal-title":"Food Funct"},{"key":"2289_CR17","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.1073\/pnas.0607296104","volume":"104","author":"BJ McMillan","year":"2007","unstructured":"McMillan BJ, Bradfield CA (2007) The aryl hydrocarbon receptor is activated by modified low-density lipoprotein. Proc Natl Acad Sci USA 104:1412\u20131417. https:\/\/doi.org\/10.1073\/pnas.0607296104","journal-title":"Proc Natl Acad Sci USA"},{"key":"2289_CR18","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1146\/annurev-immunol-032713-120245","volume":"32","author":"B Stockinger","year":"2014","unstructured":"Stockinger B, Di Meglio P, Gialitakis M, Duarte JH (2014) The aryl hydrocarbon receptor: multitasking in the immune system. Annu Rev Immunol 32:403\u2013432. https:\/\/doi.org\/10.1146\/annurev-immunol-032713-120245","journal-title":"Annu Rev Immunol"},{"key":"2289_CR19","doi-asserted-by":"publisher","first-page":"589","DOI":"10.3390\/cancers11050589","volume":"11","author":"CF Vogel","year":"2019","unstructured":"Vogel CF, Ishihara Y, Campbell CE, Kado SY, Nguyen-Chi A, Sweeney C, Pollet M, Haarmann-Stemmann T, Tuscano JM (2019) A protective role of aryl hydrocarbon receptor repressor in inflammation and tumor growth. Cancers (Basel) 11:589. https:\/\/doi.org\/10.3390\/cancers11050589","journal-title":"Cancers (Basel)"},{"key":"2289_CR20","doi-asserted-by":"publisher","first-page":"2941","DOI":"10.1210\/me.2007-0211","volume":"21","author":"CF Vogel","year":"2007","unstructured":"Vogel CF, Sciullo E, Li W, Wong P, Lazennec G, Matsumura F (2007) RelB, a new partner of aryl hydrocarbon receptor-mediated transcription. Mol Endocrinol 21:2941\u20132955. https:\/\/doi.org\/10.1210\/me.2007-0211","journal-title":"Mol Endocrinol"},{"key":"2289_CR21","doi-asserted-by":"publisher","first-page":"3263","DOI":"10.1091\/mbc.e08-04-0359","volume":"19","author":"JL Marlowe","year":"2008","unstructured":"Marlowe JL, Fan Y, Chang X, Peng L, Knudsen ES, Xia Y, Puga A (2008) The aryl hydrocarbon receptor binds to E2F1 and inhibits E2F1-induced apoptosis. Mol Biol Cell 19:3263\u20133271. https:\/\/doi.org\/10.1091\/mbc.e08-04-0359","journal-title":"Mol Biol Cell"},{"key":"2289_CR22","doi-asserted-by":"publisher","first-page":"1811","DOI":"10.1038\/onc.2012.197","volume":"32","author":"C Tomkiewicz","year":"2013","unstructured":"Tomkiewicz C, Herry L, Bui LC, Metayer C, Bourdeloux M, Barouki R, Coumoul X (2013) The aryl hydrocarbon receptor regulates focal adhesion sites through a non-genomic FAK\/Src pathway. Oncogene 32:1811\u20131820. https:\/\/doi.org\/10.1038\/onc.2012.197","journal-title":"Oncogene"},{"key":"2289_CR23","doi-asserted-by":"publisher","first-page":"497","DOI":"10.3389\/fimmu.2014.00497","volume":"5","author":"MT Pallotta","year":"2014","unstructured":"Pallotta MT, Fallarino F, Matino D, Macchiarulo A, Orabona C (2014) AhR-mediated, non-genomic modulation of IDO1 function. Front Immunol 5:497. https:\/\/doi.org\/10.3389\/fimmu.2014.00497","journal-title":"Front Immunol"},{"key":"2289_CR24","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1124\/pr.114.009001","volume":"67","author":"C Esser","year":"2015","unstructured":"Esser C, Rannug A (2015) The aryl hydrocarbon receptor in barrier organ physiology, immunology, and toxicology. Pharmacol Rev 67:259\u2013279. https:\/\/doi.org\/10.1124\/pr.114.009001","journal-title":"Pharmacol Rev"},{"key":"2289_CR25","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1038\/s41385-018-0019-2","volume":"11","author":"B Lamas","year":"2018","unstructured":"Lamas B, Natividad JM, Sokol H (2018) Aryl hydrocarbon receptor and intestinal immunity. Mucosal Immunol 11:1024\u20131038. https:\/\/doi.org\/10.1038\/s41385-018-0019-2","journal-title":"Mucosal Immunol"},{"key":"2289_CR26","doi-asserted-by":"publisher","first-page":"2351","DOI":"10.1016\/j.stemcr.2021.08.002","volume":"16","author":"A Nacarino-Palma","year":"2021","unstructured":"Nacarino-Palma A, Gonzalez-Rico FJ, Rejano-Gordillo CM, Ordiales-Talavero A, Merino JM, Fernandez-Salguero PM (2021) The aryl hydrocarbon receptor promotes differentiation during mouse preimplantational embryo development. Stem Cell Reports 16:2351\u20132363. https:\/\/doi.org\/10.1016\/j.stemcr.2021.08.002","journal-title":"Stem Cell Reports"},{"key":"2289_CR27","doi-asserted-by":"publisher","first-page":"970","DOI":"10.1089\/scd.2021.0096","volume":"30","author":"KL Vaughan","year":"2021","unstructured":"Vaughan KL, Franchini AM, Kern HG, Lawrence BP (2021) The aryl hydrocarbon receptor modulates murine hematopoietic stem cell homeostasis and influences lineage-biased stem and progenitor cells. Stem Cells Dev 30:970\u2013980. https:\/\/doi.org\/10.1089\/scd.2021.0096","journal-title":"Stem Cells Dev"},{"key":"2289_CR28","doi-asserted-by":"publisher","unstructured":"Wei GZ, Martin KA, Xing PY, Agrawal R, Whiley L, Wood TK, Hejndorf S, Ng YZ, Low JZY, Rossant J et al (2021) Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor. Proc Natl Acad Sci USA 118:e2021091118. https:\/\/doi.org\/10.1073\/pnas.2021091118","DOI":"10.1073\/pnas.2021091118"},{"key":"2289_CR29","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.3390\/ijms21062195","volume":"21","author":"HR Kim","year":"2020","unstructured":"Kim HR, Kang SY, Kim HO, Park CW, Chung BY (2020) Role of aryl hydrocarbon receptor activation and autophagy in psoriasis-related inflammation. Int J Mol Sci 21:2195. https:\/\/doi.org\/10.3390\/ijms21062195","journal-title":"Int J Mol Sci"},{"key":"2289_CR30","doi-asserted-by":"publisher","unstructured":"Kondrikov D, Elmansi A, Bragg RT, Mobley T, Barrett T, Eisa N, Kondrikova G, Schoeinlein P, Aguilar-Perez A, Shi XM, Fulzele S et al (2020) Kynurenine inhibits autophagy and promotes senescence in aged bone marrow mesenchymal stem cells through the aryl hydrocarbon receptor pathway. Exp Gerontol 130:110805. https:\/\/doi.org\/10.1016\/j.exger.2019.110805","DOI":"10.1016\/j.exger.2019.110805"},{"key":"2289_CR31","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1515\/BC.2006.144","volume":"387","author":"JM Hillegass","year":"2006","unstructured":"Hillegass JM, Murphy KA, Villano CM, White LA (2006) The impact of aryl hydrocarbon receptor signaling on matrix metabolism: implications for development and disease. Biol Chem 387:1159\u20131173. https:\/\/doi.org\/10.1515\/BC.2006.144","journal-title":"Biol Chem"},{"key":"2289_CR32","doi-asserted-by":"publisher","first-page":"19618","DOI":"10.1038\/srep19618","volume":"6","author":"A Eckers","year":"2016","unstructured":"Eckers A, Jakob S, Heiss C, Haarmann-Stemmann T, Goy C, Brinkmann V, Cortese-Krott MM, Sansone R, Esser C et al (2016) The aryl hydrocarbon receptor promotes aging phenotypes across species. Sci Rep 6:19618. https:\/\/doi.org\/10.1038\/srep19618","journal-title":"Sci Rep"},{"key":"2289_CR33","doi-asserted-by":"publisher","first-page":"2729","DOI":"10.3390\/cells10102729","volume":"10","author":"ES Ojo","year":"2021","unstructured":"Ojo ES, Tischkau SA (2021) The Role of AhR in the hallmarks of brain aging: friend and foe. Cells 10:2729. https:\/\/doi.org\/10.3390\/cells10102729","journal-title":"Cells"},{"key":"2289_CR34","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1172\/JCI76304","volume":"125","author":"EA Mayer","year":"2015","unstructured":"Mayer EA, Tillisch K, Gupta A (2015) Gut\/brain axis and the microbiota. J Clin Invest 125:926\u2013938. https:\/\/doi.org\/10.1172\/JCI76304","journal-title":"J Clin Invest"},{"key":"2289_CR35","doi-asserted-by":"publisher","first-page":"49","DOI":"10.3389\/fnins.2018.00049","volume":"12","author":"B Bonaz","year":"2018","unstructured":"Bonaz B, Bazin T, Pellissier S (2018) The Vagus nerve at the interface of the microbiota-gut-brain axis. Front Neurosci 12:49. https:\/\/doi.org\/10.3389\/fnins.2018.00049","journal-title":"Front Neurosci"},{"key":"2289_CR36","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.conb.2019.12.003","volume":"62","author":"LM Frankiensztajn","year":"2020","unstructured":"Frankiensztajn LM, Elliott E, Koren O (2020) The microbiota and the hypothalamus-pituitary-adrenocortical (HPA) axis, implications for anxiety and stress disorders. Curr Opin Neurobiol 62:76\u201382. https:\/\/doi.org\/10.1016\/j.conb.2019.12.003","journal-title":"Curr Opin Neurobiol"},{"key":"2289_CR37","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3389\/fcimb.2018.00013","volume":"8","author":"J Gao","year":"2018","unstructured":"Gao J, Xu K, Liu H, Liu G, Bai M, Peng C, Li T, Yin Y (2018) Impact of the gut microbiota on intestinal immunity mediated by tryptophan metabolism. Front Cell Infect Microbiol 8:13. https:\/\/doi.org\/10.3389\/fcimb.2018.00013","journal-title":"Front Cell Infect Microbiol"},{"key":"2289_CR38","doi-asserted-by":"publisher","first-page":"2655","DOI":"10.1038\/s41467-018-05184-7","volume":"9","author":"MA Jackson","year":"2018","unstructured":"Jackson MA, Verdi S, Maxan ME, Shin CM, Zierer J, Bowyer RCE, Martin T, Williams FMK, Menni C, Bell JT et al (2018) Gut microbiota associations with common diseases and prescription medications in a population-based cohort. Nat Commun 9:2655. https:\/\/doi.org\/10.1038\/s41467-018-05184-7","journal-title":"Nat Commun"},{"key":"2289_CR39","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1038\/s12276-021-00703-x","volume":"53","author":"J Park","year":"2021","unstructured":"Park J, Kim CH (2021) Regulation of common neurological disorders by gut microbial metabolites. Exp Mol Med 53:1821\u20131833. https:\/\/doi.org\/10.1038\/s12276-021-00703-x","journal-title":"Exp Mol Med"},{"key":"2289_CR40","doi-asserted-by":"publisher","first-page":"228","DOI":"10.3390\/nu13010228","volume":"13","author":"L Wu","year":"2021","unstructured":"Wu L, Han Y, Zheng Z, Peng G, Liu P, Yue S, Zhu S, Chen J, Lv H, Shao L et al (2021) Altered gut microbial metabolites in amnestic mild cognitive impairment and Alzheimer\u2019s disease: signals in host-microbe interplay. Nutrients 13:228. https:\/\/doi.org\/10.3390\/nu13010228","journal-title":"Nutrients"},{"key":"2289_CR41","doi-asserted-by":"publisher","first-page":"3683","DOI":"10.4049\/jimmunol.1701734","volume":"201","author":"R Aoki","year":"2018","unstructured":"Aoki R, Aoki-Yoshida A, Suzuki C, Takayama Y (2018) Indole-3-pyruvic acid, an aryl hydrocarbon receptor activator, suppresses experimental colitis in mice. J Immunol 201:3683\u20133693. https:\/\/doi.org\/10.4049\/jimmunol.1701734","journal-title":"J Immunol"},{"key":"2289_CR42","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/s13195-019-0551-7","volume":"11","author":"V van der Velpen","year":"2019","unstructured":"van der Velpen V, Teav T, Gallart-Ayala H, Mehl F, Konz I, Clark C, Oikonomidi A, Peyratout G, Henry H, Delorenzi M et al (2019) Systemic and central nervous system metabolic alterations in Alzheimer\u2019s disease. Alzheimers Res Ther 11:93. https:\/\/doi.org\/10.1186\/s13195-019-0551-7","journal-title":"Alzheimers Res Ther"},{"key":"2289_CR43","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s13195-020-00741-z","volume":"13","author":"L Whiley","year":"2021","unstructured":"Whiley L, Chappell KE, D\u2019Hondt E, Lewis MR, Jimenez B, Snowden SG, Soininen H, Kloszewska I, Mecocci P, Tsolaki M et al (2021) Metabolic phenotyping reveals a reduction in the bioavailability of serotonin and kynurenine pathway metabolites in both the urine and serum of individuals living with Alzheimer\u2019s disease. Alzheimers Res Ther 13:20. https:\/\/doi.org\/10.1186\/s13195-020-00741-z","journal-title":"Alzheimers Res Ther"},{"key":"2289_CR44","doi-asserted-by":"publisher","unstructured":"Teruya T, Chen YJ, Kondoh H, Fukuji Y, Yanagida M (2021) Whole-blood metabolomics of dementia patients reveal classes of disease-linked metabolites. Proc Natl Acad Sci USA 118:e2022857118. https:\/\/doi.org\/10.1073\/pnas.2022857118","DOI":"10.1073\/pnas.2022857118"},{"key":"2289_CR45","doi-asserted-by":"publisher","first-page":"1337","DOI":"10.3233\/JAD-180176","volume":"63","author":"ZQ Zhuang","year":"2018","unstructured":"Zhuang ZQ, Shen LL, Li WW, Fu X, Zeng F, Gui L, L\u00fc Y, Cai M, Zhu C, Tan YL et al (2018) Gut microbiota is altered in patients with Alzheimer\u2019s disease. J Alzheimers Dis 63:1337\u20131346. https:\/\/doi.org\/10.3233\/JAD-180176","journal-title":"J Alzheimers Dis"},{"key":"2289_CR46","doi-asserted-by":"publisher","first-page":"41802","DOI":"10.1038\/srep41802","volume":"7","author":"T Harach","year":"2017","unstructured":"Harach T, Marungruang N, Duthilleul N, Cheatham V, Mc Coy KD, Frisoni G, Neher JJ, Fak F, Jucker M, Lasser T et al (2017) Reduction of A\u03b2 amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota. Sci Rep 7:41802. https:\/\/doi.org\/10.1038\/srep41802","journal-title":"Sci Rep"},{"key":"2289_CR47","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1136\/gutjnl-2018-317431","volume":"69","author":"MS Kim","year":"2020","unstructured":"Kim MS, Kim Y, Choi H, Kim W, Park S, Lee D, Kim DK, Kim HJ, Choi H, Hyun DW et al (2020) Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer\u2019s disease animal model. Gut 69:283\u2013294. https:\/\/doi.org\/10.1136\/gutjnl-2018-317431","journal-title":"Gut"},{"key":"2289_CR48","doi-asserted-by":"publisher","first-page":"30028","DOI":"10.1038\/srep30028","volume":"6","author":"MR Minter","year":"2016","unstructured":"Minter MR, Zhang C, Leone V, Ringus DL, Zhang X, Oyler-Castrillo P, Musch MW, Liao F, Ward JF, Holtzman DM et al (2016) Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer\u2019s disease. Sci Rep 6:30028. https:\/\/doi.org\/10.1038\/srep30028","journal-title":"Sci Rep"},{"key":"2289_CR49","doi-asserted-by":"publisher","unstructured":"Ligezka AN, Sonmez AI, Corral-Frias MP, Golebiowski R, Lynch B, Croarkin PE, Romanowicz M (2021) A systematic review of microbiome changes and impact of probiotic supplementation in children and adolescents with neuropsychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry 108:110187. https:\/\/doi.org\/10.1016\/j.pnpbp.2020.110187","DOI":"10.1016\/j.pnpbp.2020.110187"},{"key":"2289_CR50","doi-asserted-by":"publisher","unstructured":"Xiang S, Ji JL, Li S, Cao XP, Xu W, Tan L, Tan CC (2022) Efficacy and safety of probiotics for the treatment of Alzheimer\u2019s disease, mild cognitive impairment, and Parkinson\u2019s disease: a systematic review and meta-analysis. Front Aging Neurosci 14:730036. https:\/\/doi.org\/10.3389\/fnagi.2022.730036","DOI":"10.3389\/fnagi.2022.730036"},{"key":"2289_CR51","doi-asserted-by":"publisher","unstructured":"de Rijke TJ, Doting MHE, van Hemert S, De Deyn PP, van Munster BC, Harmsen HJM, Sommer IEC (2022) A systematic review on the effects of different types of probiotics in animal Alzheimer\u2019s disease studies. Front Psychiatry 13:879491. https:\/\/doi.org\/10.3389\/fpsyt.2022.879491","DOI":"10.3389\/fpsyt.2022.879491"},{"key":"2289_CR52","doi-asserted-by":"publisher","unstructured":"Frausto DM, Forsyth CB, Keshavarzian A, Voigt RM (2021) Dietary regulation of gut-brain axis in Alzheimer\u2019s disease: Importance of microbiota metabolites. Front Neurosci 15:736814 https:\/\/doi.org\/10.3389\/fnins.2021.736814","DOI":"10.3389\/fnins.2021.736814"},{"key":"2289_CR53","doi-asserted-by":"publisher","first-page":"2310","DOI":"10.3390\/microorganisms9112310","volume":"9","author":"JW Kang","year":"2021","unstructured":"Kang JW, Zivkovic AM (2021) The potential utility of prebiotics to modulate Alzheimer\u2019s disease: a review of the evidence. Microorganisms 9:2310. https:\/\/doi.org\/10.3390\/microorganisms9112310","journal-title":"Microorganisms"},{"key":"2289_CR54","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1002\/ana.20854","volume":"59","author":"N Scarmeas","year":"2006","unstructured":"Scarmeas N, Stern Y, Tang MX, Mayeux R, Luchsinger JA (2006) Mediterranean diet and risk for Alzheimer\u2019s disease. Ann Neurol 59:912\u2013921. https:\/\/doi.org\/10.1002\/ana.20854","journal-title":"Ann Neurol"},{"key":"2289_CR55","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3390\/nu13010007","volume":"13","author":"G Merra","year":"2020","unstructured":"Merra G, Noce A, Marrone G, Cintoni M, Tarsitano MG, Capacci A, De Lorenzo A (2020) Influence of Mediterranean diet on human gut microbiota. Nutrients 13:7. https:\/\/doi.org\/10.3390\/nu13010007","journal-title":"Nutrients"},{"key":"2289_CR56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/19490976.2020.1788899","volume":"12","author":"F Dong","year":"2020","unstructured":"Dong F, Hao F, Murray IA, Smith PB, Koo I, Tindall AM, Kris-Etherton PM, Gowda K, Amin SG, Patterson AD et al (2020) Intestinal microbiota-derived tryptophan metabolites are predictive of Ah receptor activity. Gut Microbes 12:1\u201324. https:\/\/doi.org\/10.1080\/19490976.2020.1788899","journal-title":"Gut Microbes"},{"key":"2289_CR57","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1016\/j.chom.2018.05.003","volume":"23","author":"A Agus","year":"2018","unstructured":"Agus A, Planchais J, Sokol H (2018) Gut microbiota regulation of tryptophan metabolism in health and disease. Cell Host Microbe 23:716\u2013724. https:\/\/doi.org\/10.1016\/j.chom.2018.05.003","journal-title":"Cell Host Microbe"},{"key":"2289_CR58","doi-asserted-by":"publisher","first-page":"2973","DOI":"10.3390\/ijms22062973","volume":"22","author":"W Roth","year":"2021","unstructured":"Roth W, Zadeh K, Vekariya R, Ge Y, Mohamadzadeh M (2021) Tryptophan metabolism and gut-brain homeostasis. Int J Mol Sci 22:2973. https:\/\/doi.org\/10.3390\/ijms22062973","journal-title":"Int J Mol Sci"},{"key":"2289_CR59","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1002\/jnr.22030","volume":"87","author":"IK Hwang","year":"2009","unstructured":"Hwang IK, Yoo KY, Li H, Park OK, Lee CH, Choi JH, Jeong YG, Lee YL, Kim YM, Kwon YG et al (2009) Indole-3-propionic acid attenuates neuronal damage and oxidative stress in the ischemic hippocampus. J Neurosci Res 87:2126\u20132137. https:\/\/doi.org\/10.1002\/jnr.22030","journal-title":"J Neurosci Res"},{"key":"2289_CR60","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1111\/joim.12892","volume":"286","author":"T Hendrikx","year":"2019","unstructured":"Hendrikx T, Schnabl B (2019) Indoles: metabolites produced by intestinal bacteria capable of controlling liver disease manifestation. J Intern Med 286:32\u201340. https:\/\/doi.org\/10.1111\/joim.12892","journal-title":"J Intern Med"},{"key":"2289_CR61","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1111\/j.1574-6976.2009.00204.x","volume":"34","author":"JH Lee","year":"2010","unstructured":"Lee JH, Lee J (2010) Indole as an intercellular signal in microbial communities. FEMS Microbiol Rev 34:426\u2013444. https:\/\/doi.org\/10.1111\/j.1574-6976.2009.00204.x","journal-title":"FEMS Microbiol Rev"},{"key":"2289_CR62","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1080\/10408444.2018.1493086","volume":"48","author":"A Rannug","year":"2018","unstructured":"Rannug A, Rannug U (2018) The tryptophan derivative 6-formylindolo[3,2-b]carbazole, FICZ, a dynamic mediator of endogenous aryl hydrocarbon receptor signaling, balances cell growth and differentiation. Crit Rev Toxicol 48:555\u2013574. https:\/\/doi.org\/10.1080\/10408444.2018.1493086","journal-title":"Crit Rev Toxicol"},{"key":"2289_CR63","doi-asserted-by":"publisher","first-page":"5681","DOI":"10.3390\/ijms21165681","volume":"21","author":"A Rannug","year":"2020","unstructured":"Rannug A (2020) How the AHR became important in intestinal homeostasis-a diurnal FICZ\/AHR\/CYP1A1 feedback controls both immunity and immunopathology. Int J Mol Sci 21:5681. https:\/\/doi.org\/10.3390\/ijms21165681","journal-title":"Int J Mol Sci"},{"key":"2289_CR64","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1021\/acs.chemrestox.5b00416","volume":"29","author":"A Smirnova","year":"2016","unstructured":"Smirnova A, Wincent E, Vikstr\u00f6m Bergander L, Alsberg T, Bergman J, Rannug A, Rannug U (2016) Evidence for new light-independent pathways for generation of the endogenous aryl hydrocarbon receptor agonist FICZ. Chem Res Toxicol 29:75\u201386. https:\/\/doi.org\/10.1021\/acs.chemrestox.5b00416","journal-title":"Chem Res Toxicol"},{"key":"2289_CR65","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.cbi.2004.08.005","volume":"149","author":"L Bergander","year":"2004","unstructured":"Bergander L, Wincent E, Rannug A, Foroozesh M, Alworth W, Rannug U (2004) Metabolic fate of the Ah receptor ligand 6-formylindolo[3,2-b]carbazole. Chem Biol Interact 149:151\u2013164. https:\/\/doi.org\/10.1016\/j.cbi.2004.08.005","journal-title":"Chem Biol Interact"},{"key":"2289_CR66","doi-asserted-by":"publisher","first-page":"4479","DOI":"10.1073\/pnas.1118467109","volume":"109","author":"E Wincent","year":"2012","unstructured":"Wincent E, Bengtsson J, Mohammadi Bardbori A, Alsberg T, Luecke S, Rannug U, Rannug A (2012) Inhibition of cytochrome P4501-dependent clearance of the endogenous agonist FICZ as a mechanism for activation of the aryl hydrocarbon receptor. Proc Natl Acad Sci USA 109:4479\u20134484. https:\/\/doi.org\/10.1073\/pnas.1118467109","journal-title":"Proc Natl Acad Sci USA"},{"key":"2289_CR67","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1007\/s12031-020-01506-x","volume":"70","author":"M Keshavarzi","year":"2020","unstructured":"Keshavarzi M, Khoshnoud MJ, Ghaffarian Bahraman A, Mohammadi-Bardbori A (2020) An endogenous ligand of aryl hydrocarbon receptor 6-formylindolo[3,2-b]carbazole (FICZ) is a signaling molecule in neurogenesis of adult hippocampal neurons. J Mol Neurosci 70:806\u2013817. https:\/\/doi.org\/10.1007\/s12031-020-01506-x","journal-title":"J Mol Neurosci"},{"key":"2289_CR68","doi-asserted-by":"publisher","first-page":"9298052","DOI":"10.1155\/2018\/9298052","volume":"2018","author":"Y Tanaka","year":"2018","unstructured":"Tanaka Y, Uchi H, Hashimoto-Hachiya A, Furue M (2018) Tryptophan photoproduct FICZ upregulates IL1A, IL1B, and IL6 expression via oxidative stress in keratinocytes. Oxid Med Cell Longev 2018:9298052. https:\/\/doi.org\/10.1155\/2018\/9298052","journal-title":"Oxid Med Cell Longev"},{"key":"2289_CR69","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.jdermsci.2017.10.002","volume":"89","author":"M Murai","year":"2018","unstructured":"Murai M, Tsuji G, Hashimoto-Hachiya A, Kawakami Y, Furue M, Mitoma C (2018) An endogenous tryptophan photo-product, FICZ, is potentially involved in photo-aging by reducing TGF-\u03b2-regulated collagen homeostasis. J Dermatol Sci 89:19\u201326. https:\/\/doi.org\/10.1016\/j.jdermsci.2017.10.002","journal-title":"J Dermatol Sci"},{"key":"2289_CR70","doi-asserted-by":"publisher","unstructured":"Kim DJ, Iwasaki A, Chien AL, Kang S (2022) UVB-mediated DNA damage induces matrix metalloproteinases to promote photoaging in an AhR- and SP1-dependent manner. JCI Insight 7:e156344. https:\/\/doi.org\/10.1172\/jci.insight.156344","DOI":"10.1172\/jci.insight.156344"},{"key":"2289_CR71","doi-asserted-by":"publisher","unstructured":"Marszalek-Grabska M, Walczak K, Gawel K, Wicha-Komsta K, Wnorowska S, Wnorowski A, Turski WA (2021) Kynurenine emerges from the shadows - current knowledge on its fate and function. Pharmacol Ther 225:107845. https:\/\/doi.org\/10.1016\/j.pharmthera.2021.107845","DOI":"10.1016\/j.pharmthera.2021.107845"},{"key":"2289_CR72","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.neuropharm.2016.03.024","volume":"112","author":"MD Lovelace","year":"2017","unstructured":"Lovelace MD, Varney B, Sundaram G, Lennon MJ, Lim CK, Jacobs K, Guillemin GJ, Brew BJ (2017) Recent evidence for an expanded role of the kynurenine pathway of tryptophan metabolism in neurological diseases. Neuropharmacology 112:373\u2013388. https:\/\/doi.org\/10.1016\/j.neuropharm.2016.03.024","journal-title":"Neuropharmacology"},{"key":"2289_CR73","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1038\/s41380-019-0414-4","volume":"25","author":"J Savitz","year":"2020","unstructured":"Savitz J (2020) The kynurenine pathway: a finger in every pie. Mol Psychiatry 25:131\u2013147. https:\/\/doi.org\/10.1038\/s41380-019-0414-4","journal-title":"Mol Psychiatry"},{"key":"2289_CR74","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1093\/toxsci\/kfq024","volume":"115","author":"BC DiNatale","year":"2010","unstructured":"DiNatale BC, Murray IA, Schroeder JC, Flaveny CA, Lahoti TS, Laurenzana EM, Omiecinski CJ, Perdew GH (2010) Kynurenic acid is a potent endogenous aryl hydrocarbon receptor ligand that synergistically induces interleukin-6 in the presence of inflammatory signaling. Toxicol Sci 115:89\u201397. https:\/\/doi.org\/10.1093\/toxsci\/kfq024","journal-title":"Toxicol Sci"},{"key":"2289_CR75","doi-asserted-by":"publisher","first-page":"3190","DOI":"10.4049\/jimmunol.0903670","volume":"185","author":"JD Mezrich","year":"2010","unstructured":"Mezrich JD, Fechner JH, Zhang X, Johnson BP, Burlingham WJ, Bradfield CA (2010) An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells. J Immunol 185:3190\u20133198. https:\/\/doi.org\/10.4049\/jimmunol.0903670","journal-title":"J Immunol"},{"key":"2289_CR76","doi-asserted-by":"publisher","unstructured":"Baumgartner R, Forteza MJ, Ketelhuth DFJ (2019) The interplay between cytokines and the kynurenine pathway in inflammation and atherosclerosis. Cytokine 122:154148. https:\/\/doi.org\/10.1016\/j.cyto.2017.09.004","DOI":"10.1016\/j.cyto.2017.09.004"},{"key":"2289_CR77","doi-asserted-by":"publisher","first-page":"4425","DOI":"10.1111\/j.1742-4658.2011.08366.x","volume":"278","author":"N Braidy","year":"2011","unstructured":"Braidy N, Guillemin GJ, Mansour H, Chan-Ling T, Grant R (2011) Changes in kynurenine pathway metabolism in the brain, liver and kidney of aged female Wistar rats. FEBS J 278:4425\u20134434. https:\/\/doi.org\/10.1111\/j.1742-4658.2011.08366.x","journal-title":"FEBS J"},{"key":"2289_CR78","doi-asserted-by":"publisher","unstructured":"Salminen A (2022) Role of indoleamine 2,3-dioxygenase 1 (IDO1) and kynurenine pathway in the regulation of the aging process. Ageing Res Rev 75:101573. https:\/\/doi.org\/10.1016\/j.arr.2022.101573","DOI":"10.1016\/j.arr.2022.101573"},{"key":"2289_CR79","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1186\/s12974-019-1567-4","volume":"16","author":"P Chatterjee","year":"2019","unstructured":"Chatterjee P, Zetterberg H, Goozee K, Lim CK, Jacobs KR, Ashton NJ, Hye A, Pedrini S, Sohrabi HR, Shah T et al (2019) Plasma neurofilament light chain and amyloid-\u03b2 are associated with the kynurenine pathway metabolites in preclinical Alzheimer\u2019s disease. J Neuroinflammation 16:186. https:\/\/doi.org\/10.1186\/s12974-019-1567-4","journal-title":"J Neuroinflammation"},{"key":"2289_CR80","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.1096\/fj.14-259598","volume":"29","author":"CS Reigstad","year":"2015","unstructured":"Reigstad CS, Salmonson CE, Rainey JF 3rd, Szurszewski JH, Linden DR, Sonnenburg JL, Farrugia G, Kashyap PC (2015) Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J 29:1395\u20131403. https:\/\/doi.org\/10.1096\/fj.14-259598","journal-title":"FASEB J"},{"key":"2289_CR81","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.cell.2015.02.047","volume":"161","author":"JM Yano","year":"2015","unstructured":"Yano JM, Yu K, Donaldson GP, Shastri GG, Ann P, Ma L, Nagler CR, Ismagilov RF, Mazmanian SK, Hsiao EY (2015) Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161:264\u2013276. https:\/\/doi.org\/10.1016\/j.cell.2015.02.047","journal-title":"Cell"},{"key":"2289_CR82","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1002\/med.21628","volume":"40","author":"N Ma","year":"2020","unstructured":"Ma N, Zhang J, Reiter RJ, Ma X (2020) Melatonin mediates mucosal immune cells, microbial metabolism, and rhythm crosstalk: a therapeutic target to reduce intestinal inflammation. Med Res Rev 40:606\u2013632. https:\/\/doi.org\/10.1002\/med.21628","journal-title":"Med Res Rev"},{"key":"2289_CR83","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1038\/s41598-018-38018-z","volume":"9","author":"AD Mandic","year":"2019","unstructured":"Mandic AD, Woting A, Jaenicke T, Sander A, Sabrowski W, Rolle-Kampcyk U, von Bergen M, Blaut M (2019) Clostridium ramosum regulates enterochromaffin cell development and serotonin release. Sci Rep 9:1177. https:\/\/doi.org\/10.1038\/s41598-018-38018-z","journal-title":"Sci Rep"},{"key":"2289_CR84","doi-asserted-by":"publisher","unstructured":"Huang F, Wu X (2021) Brain neurotransmitter modulation by gut microbiota in anxiety and depression. Front Cell Dev Biol 9:649103. https:\/\/doi.org\/10.3389\/fcell.2021.649103","DOI":"10.3389\/fcell.2021.649103"},{"key":"2289_CR85","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.phrs.2018.06.015","volume":"140","author":"H Wu","year":"2019","unstructured":"Wu H, Denna TH, Storkersen JN, Gerriets VA (2019) Beyond a neurotransmitter: the role of serotonin in inflammation and immunity. Pharmacol Res 140:100\u2013114. https:\/\/doi.org\/10.1016\/j.phrs.2018.06.015","journal-title":"Pharmacol Res"},{"key":"2289_CR86","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1111\/febs.14026","volume":"284","author":"Y Li","year":"2017","unstructured":"Li Y, Hu N, Yang D, Oxenkrug G, Yang Q (2017) Regulating the balance between the kynurenine and serotonin pathways of tryptophan metabolism. FEBS J 284:948\u2013966. https:\/\/doi.org\/10.1111\/febs.14026","journal-title":"FEBS J"},{"key":"2289_CR87","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1007\/s00204-015-1513-x","volume":"89","author":"AM Araujo","year":"2015","unstructured":"Araujo AM, Carvalho F, Bastos Mde L, Guedes de Pinho P, Carvalho M (2015) The hallucinogenic world of tryptamines: an updated review. Arch Toxicol 89:1151\u20131173. https:\/\/doi.org\/10.1007\/s00204-015-1513-x","journal-title":"Arch Toxicol"},{"key":"2289_CR88","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/BF01000528","volume":"8","author":"DD Mousseau","year":"1993","unstructured":"Mousseau DD (1993) Tryptamine: a metabolite of tryptophan implicated in various neuropsychiatric disorders. Metab Brain Dis 8:1\u201344. https:\/\/doi.org\/10.1007\/BF01000528","journal-title":"Metab Brain Dis"},{"key":"2289_CR89","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1385\/nmm:9:1:55","volume":"9","author":"EL Paley","year":"2007","unstructured":"Paley EL, Denisova G, Sokolova O, Posternak N, Wang X, Brownell AL (2007) Tryptamine induces tryptophanyl-tRNA synthetase-mediated neurodegeneration with neurofibrillary tangles in human cell and mouse models. Neuromolecular Med 9:55\u201382. https:\/\/doi.org\/10.1385\/nmm:9:1:55","journal-title":"Neuromolecular Med"},{"key":"2289_CR90","doi-asserted-by":"publisher","unstructured":"Dopkins N, Becker W, Miranda K, Walla M, Nagarkatti P, Nagarkatti M (2021) Tryptamine attenuates experimental multiple sclerosis through activation of aryl hydrocarbon receptor. Front Pharmacol 11:619265. https:\/\/doi.org\/10.3389\/fphar.2020.619265","DOI":"10.3389\/fphar.2020.619265"},{"key":"2289_CR91","doi-asserted-by":"publisher","first-page":"1522","DOI":"10.1124\/dmd.115.064246","volume":"43","author":"TD Hubbard","year":"2015","unstructured":"Hubbard TD, Murray IA, Perdew GH (2015) Indole and tryptophan metabolism: endogenous and dietary routes to Ah receptor activation. Drug Metab Dispos 43:1522\u20131535. https:\/\/doi.org\/10.1124\/dmd.115.064246","journal-title":"Drug Metab Dispos"},{"key":"2289_CR92","doi-asserted-by":"publisher","first-page":"1536","DOI":"10.1124\/dmd.115.063677","volume":"43","author":"Y Cheng","year":"2015","unstructured":"Cheng Y, Jin UH, Allred CD, Jayaraman A, Chapkin RS, Safe S (2015) Aryl hydrocarbon receptor activity of tryptophan metabolites in young adult mouse colonocytes. Drug Metab Dispos 43:1536\u20131543. https:\/\/doi.org\/10.1124\/dmd.115.063677","journal-title":"Drug Metab Dispos"},{"key":"2289_CR93","doi-asserted-by":"publisher","first-page":"2614","DOI":"10.3390\/ijms21072614","volume":"21","author":"B Vyhlidalova","year":"2020","unstructured":"Vyhlidalova B, Krasulova K, Pecinkova P, Marcalikova A, Vrzal R, Zemankova L, Vanco J, Travnicek Z, Vondracek J, Karasova M et al (2020) Gut microbial catabolites of tryptophan are ligands and agonists of the aryl hydrocarbon receptor: a detailed characterization. Int J Mol Sci 21:2614. https:\/\/doi.org\/10.3390\/ijms21072614","journal-title":"Int J Mol Sci"},{"key":"2289_CR94","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1124\/mol.113.091165","volume":"85","author":"UH Jin","year":"2014","unstructured":"Jin UH, Lee SO, Sridharan G, Lee K, Davidson LA, Jayaraman A, Chapkin RS, Alaniz R, Safe S (2014) Microbiome-derived tryptophan metabolites and their aryl hydrocarbon receptor-dependent agonist and antagonist activities. Mol Pharmacol 85:777\u2013788. https:\/\/doi.org\/10.1124\/mol.113.091165","journal-title":"Mol Pharmacol"},{"key":"2289_CR95","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.bbrc.2008.07.156","volume":"375","author":"CF Vogel","year":"2008","unstructured":"Vogel CF, Goth SR, Dong B, Pessah IN, Matsumura F (2008) Aryl hydrocarbon receptor signaling mediates expression of indoleamine 2,3-dioxygenase. Biochem Biophys Res Commun 375:331\u2013335. https:\/\/doi.org\/10.1016\/j.bbrc.2008.07.156","journal-title":"Biochem Biophys Res Commun"},{"key":"2289_CR96","doi-asserted-by":"publisher","unstructured":"Manzella CR, Ackerman M, Singhal M, Ticho AL, Ceh J, Alrefai WA, Saksena S, Dudeja PK, Gill RK (2020) Serotonin modulates AhR activation by interfering with CYP1A1-mediated clearance of AhR ligands. Cell Physiol Biochem 54:126\u2013141. https:\/\/doi.org\/10.33594\/000000209","DOI":"10.33594\/000000209"},{"key":"2289_CR97","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1097\/MOG.0b013e32835c9cb3","volume":"29","author":"MA Ciorba","year":"2013","unstructured":"Ciorba MA (2013) Indoleamine 2,3 dioxygenase in intestinal disease. Curr Opin Gastroenterol 29:146\u2013152. https:\/\/doi.org\/10.1097\/MOG.0b013e32835c9cb3","journal-title":"Curr Opin Gastroenterol"},{"key":"2289_CR98","doi-asserted-by":"publisher","first-page":"1471","DOI":"10.1093\/ibd\/izy103","volume":"24","author":"MA Sofia","year":"2018","unstructured":"Sofia MA, Ciorba MA, Meckel K, Lim CK, Guillemin GJ, Weber CR, Bissonnette M, Pekow JR (2018) Tryptophan metabolism through the kynurenine pathway is associated with endoscopic inflammation in ulcerative colitis. Inflamm Bowel Dis 24:1471\u20131480. https:\/\/doi.org\/10.1093\/ibd\/izy103","journal-title":"Inflamm Bowel Dis"},{"key":"2289_CR99","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1007\/978-1-4615-0135-0_46","volume":"527","author":"CM Forrest","year":"2003","unstructured":"Forrest CM, Gould SR, Darlington LG, Stone TW (2003) Levels of purine, kynurenine and lipid peroxidation products in patients with inflammatory bowel disease. Adv Exp Med Biol 527:395\u2013400. https:\/\/doi.org\/10.1007\/978-1-4615-0135-0_46","journal-title":"Adv Exp Med Biol"},{"key":"2289_CR100","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1002\/ibd.21849","volume":"18","author":"NK Gupta","year":"2012","unstructured":"Gupta NK, Thaker AI, Kanuri N, Riehl TE, Rowley CW, Stenson WF, Ciorba MA (2012) Serum analysis of tryptophan catabolism pathway: correlation with Crohn\u2019s disease activity. Inflamm Bowel Dis 18:1214\u20131220. https:\/\/doi.org\/10.1002\/ibd.21849","journal-title":"Inflamm Bowel Dis"},{"key":"2289_CR101","doi-asserted-by":"publisher","first-page":"2574","DOI":"10.4049\/jimmunol.1400833","volume":"193","author":"J Yu","year":"2014","unstructured":"Yu J, Wang Y, Yan F, Zhang P, Li H, Zhao H, Yan C, Yan F, Ren X (2014) Noncanonical NF-\u03baB activation mediates STAT3-stimulated IDO upregulation in myeloid-derived suppressor cells in breast cancer. J Immunol 193:2574\u20132586. https:\/\/doi.org\/10.4049\/jimmunol.1400833","journal-title":"J Immunol"},{"key":"2289_CR102","doi-asserted-by":"publisher","first-page":"2007","DOI":"10.1111\/j.1471-4159.1991.tb03460.x","volume":"56","author":"S Fukui","year":"1991","unstructured":"Fukui S, Schwarcz R, Rapoport SI, Takada Y, Smith QR (1991) Blood-brain barrier transport of kynurenines: implications for brain synthesis and metabolism. J Neurochem 56:2007\u20132017. https:\/\/doi.org\/10.1111\/j.1471-4159.1991.tb03460.x","journal-title":"J Neurochem"},{"key":"2289_CR103","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1136\/gutjnl-2020-320789","volume":"70","author":"B Zhang","year":"2021","unstructured":"Zhang B, Wang HE, Bai YM, Tsai SJ, Su TP, Chen TJ, Wang YP, Chen MH (2021) Inflammatory bowel disease is associated with higher dementia risk: a nationwide longitudinal study. Gut 70:85\u201391. https:\/\/doi.org\/10.1136\/gutjnl-2020-320789","journal-title":"Gut"},{"key":"2289_CR104","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0000000000001714","author":"M Aggarwal","year":"2022","unstructured":"Aggarwal M, Alkhayyat M, Abou Saleh M, Sarmini MT, Singh A, Garg R, Garg P, Mansoor E, Padival R, Cohen BL (2022) Alzheimer disease occurs more frequently in patients with inflammatory bowel disease: insight from a nationwide study. J Clin Gastroenterol. https:\/\/doi.org\/10.1097\/MCG.0000000000001714","journal-title":"J Clin Gastroenterol"},{"key":"2289_CR105","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1093\/ecco-jcc\/jjab162","volume":"16","author":"GH Kim","year":"2022","unstructured":"Kim GH, Lee YC, Kim TJ, Kim ER, Hong SN, Chang DK, Kim YH (2022) Risk of neurodegenerative diseases in patients with inflammatory bowel disease: a nationwide population-based cohort study. J Crohns Colitis 16:436\u2013443. https:\/\/doi.org\/10.1093\/ecco-jcc\/jjab162","journal-title":"J Crohns Colitis"},{"key":"2289_CR106","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1111\/j.1471-4159.2008.05241.x","volume":"105","author":"R Owe-Young","year":"2008","unstructured":"Owe-Young R, Webster NL, Mukhtar M, Pomerantz RJ, Smythe G, Walker D, Armati PJ, Crowe SM, Brew BJ (2008) Kynurenine pathway metabolism in human blood-brain-barrier cells: implications for immune tolerance and neurotoxicity. J Neurochem 105:1346\u20131357. https:\/\/doi.org\/10.1111\/j.1471-4159.2008.05241.x","journal-title":"J Neurochem"},{"key":"2289_CR107","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.bbi.2020.04.016","volume":"88","author":"Q Zhang","year":"2020","unstructured":"Zhang Q, Sun Y, He Z, Xu Y, Li X, Ding J, Lu M, Hu G (2020) Kynurenine regulates NLRP2 inflammasome in astrocytes and its implications in depression. Brain Behav Immun 88:471\u2013481. https:\/\/doi.org\/10.1016\/j.bbi.2020.04.016","journal-title":"Brain Behav Immun"},{"issue":"Pt B","key":"2289_CR108","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1016\/j.neuropharm.2016.07.002","volume":"112","author":"PJ Kennedy","year":"2017","unstructured":"Kennedy PJ, Cryan JF, Dinan TG, Clarke G (2017) Kynurenine pathway metabolism and the microbiota-gut-brain axis. Neuropharmacology 112(Pt B):399\u2013412. https:\/\/doi.org\/10.1016\/j.neuropharm.2016.07.002","journal-title":"Neuropharmacology"},{"key":"2289_CR109","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/BF03226377","volume":"26","author":"E Banoglu","year":"2001","unstructured":"Banoglu E, Jha GG, King RS (2001) Hepatic microsomal metabolism of indole to indoxyl, a precursor of indoxyl sulfate. Eur J Drug Metab Pharmacokinet 26:235\u2013240. https:\/\/doi.org\/10.1007\/BF03226377","journal-title":"Eur J Drug Metab Pharmacokinet"},{"key":"2289_CR110","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1007\/BF03190428","volume":"27","author":"E Banoglu","year":"2002","unstructured":"Banoglu E, King RS (2002) Sulfation of indoxyl by human and rat aryl (phenol) sulfotransferases to form indoxyl sulfate. Eur J Drug Metab Pharmacokinet 27:135\u2013140. https:\/\/doi.org\/10.1007\/BF03190428","journal-title":"Eur J Drug Metab Pharmacokinet"},{"key":"2289_CR111","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1111\/hdi.12483","volume":"21","author":"X Tan","year":"2017","unstructured":"Tan X, Cao X, Zou J, Shen B, Zhang X, Liu Z, Lv W, Teng J, Ding X (2017) Indoxyl sulfate, a valuable biomarker in chronic kidney disease and dialysis. Hemodial Int 21:161\u2013167. https:\/\/doi.org\/10.1111\/hdi.12483","journal-title":"Hemodial Int"},{"key":"2289_CR112","doi-asserted-by":"publisher","first-page":"252","DOI":"10.3390\/toxins13040252","volume":"13","author":"J Rysz","year":"2021","unstructured":"Rysz J, Franczyk B, Lawinski J, Olszewski R, Cialkowska-Rysz A, Gluba-Brzozka A (2021) The impact of CKD on uremic toxins and gut microbiota. Toxins (Basel) 13:252. https:\/\/doi.org\/10.3390\/toxins13040252","journal-title":"Toxins (Basel)"},{"key":"2289_CR113","doi-asserted-by":"publisher","first-page":"1998","DOI":"10.1046\/j.1471-4159.1998.70051998.x","volume":"70","author":"R Carpenedo","year":"1998","unstructured":"Carpenedo R, Mannaioni G, Moroni F (1998) Oxindole, a sedative tryptophan metabolite, accumulates in blood and brain of rats with acute hepatic failure. J Neurochem 70:1998\u20132003. https:\/\/doi.org\/10.1046\/j.1471-4159.1998.70051998.x","journal-title":"J Neurochem"},{"key":"2289_CR114","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1681\/ASN.2013121283","volume":"26","author":"L Dou","year":"2015","unstructured":"Dou L, Sallee M, Cerini C, Poitevin S, Gondouin B, Jourde-Chiche N, Fallague K, Brunet P, Calaf R, Dussol B, Mallet B, Dignat-George F, Burtey S (2015) The cardiovascular effect of the uremic solute indole-3 acetic acid. J Am Soc Nephrol 26:876\u2013887. https:\/\/doi.org\/10.1681\/ASN.2013121283","journal-title":"J Am Soc Nephrol"},{"key":"2289_CR115","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/j.kint.2019.09.029","volume":"97","author":"JA Walker","year":"2020","unstructured":"Walker JA, Richards S, Belghasem ME, Arinze N, Yoo SB, Tashjian JY, Whelan SA, Lee N, Kolachalama VB, Francis J, Ravid K, Sherr D, Chitalia VC (2020) Temporal and tissue-specific activation of aryl hydrocarbon receptor in discrete mouse models of kidney disease. Kidney Int 97:538\u2013550. https:\/\/doi.org\/10.1016\/j.kint.2019.09.029","journal-title":"Kidney Int"},{"key":"2289_CR116","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1111\/j.1365-2125.2005.02389.x","volume":"60","author":"M Th\u00f6rn","year":"2005","unstructured":"Th\u00f6rn M, Finnstr\u00f6m N, Lundgren S, Rane A, L\u00f6\u00f6f L (2005) Cytochromes P450 and MDR1 mRNA expression along the human gastrointestinal tract. Br J Clin Pharmacol 60:54\u201360. https:\/\/doi.org\/10.1111\/j.1365-2125.2005.02389.x","journal-title":"Br J Clin Pharmacol"},{"key":"2289_CR117","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1042\/BJ20061431","volume":"404","author":"W Teubner","year":"2007","unstructured":"Teubner W, Meinl W, Florian S, Kretzschmar M, Glatt H (2007) Identification and localization of soluble sulfotransferases in the human gastrointestinal tract. Biochem J 404:207\u2013215. https:\/\/doi.org\/10.1042\/BJ20061431","journal-title":"Biochem J"},{"key":"2289_CR118","doi-asserted-by":"publisher","first-page":"21011","DOI":"10.1038\/s41598-021-99845-1","volume":"11","author":"Brydges CR, Fiehn O, Mayberg HS, Schreiber H, Dehkordi SM, Bhattacharyya S, Cha J, Choi KS, Craighead WE, Krishnan RR, Rush AJ, Dunlop BW, Kaddurah-Daouk R; Mood Disorders Precision Medicine Consortium","year":"2021","unstructured":"Brydges CR, Fiehn O, Mayberg HS, Schreiber H, Dehkordi SM, Bhattacharyya S, Cha J, Choi KS, Craighead WE, Krishnan RR et al (2021) Indoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature. Sci Rep 11:21011. https:\/\/doi.org\/10.1038\/s41598-021-99845-1","journal-title":"Sci Rep"},{"key":"2289_CR119","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1007\/s11011-020-00561-y","volume":"35","author":"CY Zhang","year":"2020","unstructured":"Zhang CY, He FF, Su H, Zhang C, Meng XF (2020) Association between chronic kidney disease and Alzheimer\u2019s disease: an update. Metab Brain Dis 35:883\u2013894. https:\/\/doi.org\/10.1007\/s11011-020-00561-y","journal-title":"Metab Brain Dis"},{"key":"2289_CR120","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.exger.2016.11.012","volume":"87","author":"T Nakagawa","year":"2017","unstructured":"Nakagawa T, Hasegawa Y, Uekawa K, Kim-Mitsuyama S (2017) Chronic kidney disease accelerates cognitive impairment in a mouse model of Alzheimer\u2019s disease, through angiotensin II. Exp Gerontol 87:108\u2013112. https:\/\/doi.org\/10.1016\/j.exger.2016.11.012","journal-title":"Exp Gerontol"},{"key":"2289_CR121","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1038\/s41581-018-0018-2","volume":"14","author":"T Yang","year":"2018","unstructured":"Yang T, Richards EM, Pepine CJ, Raizada MK (2018) The gut microbiota and the brain-gut-kidney axis in hypertension and chronic kidney disease. Nat Rev Nephrol 14:442\u2013456. https:\/\/doi.org\/10.1038\/s41581-018-0018-2","journal-title":"Nat Rev Nephrol"},{"key":"2289_CR122","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1681\/ASN.2019070728","volume":"31","author":"M Bobot","year":"2020","unstructured":"Bobot M, Thomas L, Moyon A, Fernandez S, McKay N, Balasse L, Garrigue P, Brige P, Chopinet S, Poitevin S et al (2020) Uremic toxic Blood-Brain Barrier disruption mediated by AhR activation leads to cognitive impairment during experimental renal dysfunction. J Am Soc Nephrol 31:1509\u20131521. https:\/\/doi.org\/10.1681\/ASN.2019070728","journal-title":"J Am Soc Nephrol"},{"key":"2289_CR123","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1152\/physrev.00025.2013","volume":"95","author":"SK Nigam","year":"2015","unstructured":"Nigam SK, Bush KT, Martovetsky G, Ahn SY, Liu HC, Richard E, Bhatnagar V, Wu W (2015) The organic anion transporter (OAT) family: a systems biology perspective. Physiol Rev 95:83\u2013123. https:\/\/doi.org\/10.1152\/physrev.00025.2013","journal-title":"Physiol Rev"},{"key":"2289_CR124","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1007\/s10157-011-0460-y","volume":"15","author":"K Hosoya","year":"2011","unstructured":"Hosoya K, Tachikawa M (2011) Roles of organic anion\/cation transporters at the blood-brain and blood-cerebrospinal fluid barriers involving uremic toxins. Clin Exp Nephrol 15:478\u2013485. https:\/\/doi.org\/10.1007\/s10157-011-0460-y","journal-title":"Clin Exp Nephrol"},{"key":"2289_CR125","doi-asserted-by":"publisher","first-page":"904","DOI":"10.5551\/jat.23663","volume":"21","author":"M Koizumi","year":"2014","unstructured":"Koizumi M, Tatebe J, Watanabe I, Yamazaki J, Ikeda T, Morita T (2014) Aryl hydrocarbon receptor mediates indoxyl sulfate-induced cellular senescence in human umbilical vein endothelial cells. J Atheroscler Thromb 21:904\u2013916. https:\/\/doi.org\/10.5551\/jat.23663","journal-title":"J Atheroscler Thromb"},{"key":"2289_CR126","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3390\/toxins12010058","volume":"12","author":"B Opdebeeck","year":"2020","unstructured":"Opdebeeck B, D\u2019Haese PC, Verhulst A (2020) Molecular and cellular mechanisms that induce arterial calcification by indoxyl sulfate and P-cresyl sulfate. Toxins (Basel) 12:58. https:\/\/doi.org\/10.3390\/toxins12010058","journal-title":"Toxins (Basel)"},{"key":"2289_CR127","doi-asserted-by":"publisher","first-page":"412","DOI":"10.3390\/toxins12060412","volume":"12","author":"RSD Cunha","year":"2020","unstructured":"Cunha RSD, Santos AF, Barreto FC, Stinghen AEM (2020) How do uremic toxins affect the endothelium? Toxins (Basel) 12:412. https:\/\/doi.org\/10.3390\/toxins12060412","journal-title":"Toxins (Basel)"},{"key":"2289_CR128","doi-asserted-by":"publisher","first-page":"338","DOI":"10.3390\/ijms20020338","volume":"20","author":"T Matsumoto","year":"2019","unstructured":"Matsumoto T, Takayanagi K, Kojima M, Taguchi K, Kobayashi T (2019) Acute exposure to indoxyl sulfate impairs endothelium-dependent vasorelaxation in rat aorta. Int J Mol Sci 20:338. https:\/\/doi.org\/10.3390\/ijms20020338","journal-title":"Int J Mol Sci"},{"key":"2289_CR129","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1159\/000191468","volume":"29","author":"Z Tumur","year":"2009","unstructured":"Tumur Z, Niwa T (2009) Indoxyl sulfate inhibits nitric oxide production and cell viability by inducing oxidative stress in vascular endothelial cells. Am J Nephrol 29:551\u2013557. https:\/\/doi.org\/10.1159\/000191468","journal-title":"Am J Nephrol"},{"key":"2289_CR130","doi-asserted-by":"publisher","first-page":"38869","DOI":"10.1074\/jbc.M110.166686","volume":"285","author":"S Ito","year":"2010","unstructured":"Ito S, Osaka M, Higuchi Y, Nishijima F, Ishii H, Yoshida M (2010) Indoxyl sulfate induces leukocyte-endothelial interactions through up-regulation of E-selectin. J Biol Chem 285:38869\u201338875. https:\/\/doi.org\/10.1074\/jbc.M110.166686","journal-title":"J Biol Chem"},{"key":"2289_CR131","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.3389\/fphys.2018.01623","volume":"9","author":"M Karbowska","year":"2018","unstructured":"Karbowska M, Kaminski TW, Znorko B, Domaniewski T, Misztal T, Rusak T, Pryczynicz A, Guzinska-Ustymowicz K, Pawlak K, Pawlak D (2018) Indoxyl sulfate promotes arterial thrombosis in rat model via increased levels of complex TF\/VII, PAI-1, platelet activation as well as decreased contents of SIRT1 and SIRT3. Front Physiol 9:1623. https:\/\/doi.org\/10.3389\/fphys.2018.01623","journal-title":"Front Physiol"},{"key":"2289_CR132","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/j.kint.2015.11.020","volume":"89","author":"SC Hung","year":"2016","unstructured":"Hung SC, Kuo KL, Huang HL, Lin CC, Tsai TH, Wang CH, Chen JW, Lin SJ, Huang PH, Tarng DC (2016) Indoxyl sulfate suppresses endothelial progenitor cell-mediated neovascularization. Kidney Int 89:574\u2013585. https:\/\/doi.org\/10.1016\/j.kint.2015.11.020","journal-title":"Kidney Int"},{"key":"2289_CR133","doi-asserted-by":"publisher","unstructured":"Yisireyili M, Saito S, Abudureyimu S, Adelibieke Y, Ng HY, Nishijima F, Takeshita K, Murohara T, Niwa T (2014) Indoxyl sulfate-induced activation of (pro)renin receptor promotes cell proliferation and tissue factor expression in vascular smooth muscle cells. PLoS One 9:e109268. https:\/\/doi.org\/10.1371\/journal.pone.0109268","DOI":"10.1371\/journal.pone.0109268"},{"key":"2289_CR134","doi-asserted-by":"publisher","first-page":"960","DOI":"10.5551\/jat.34462","volume":"23","author":"S Ito","year":"2016","unstructured":"Ito S, Osaka M, Edamatsu T, Itoh Y, Yoshida M (2016) Crucial role of the aryl hydrocarbon receptor (AhR) in indoxyl sulfate-induced vascular inflammation. J Atheroscler Thromb 23:960\u2013975. https:\/\/doi.org\/10.5551\/jat.34462","journal-title":"J Atheroscler Thromb"},{"key":"2289_CR135","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.phrs.2017.12.025","volume":"130","author":"T Huc","year":"2018","unstructured":"Huc T, Nowinski A, Drapala A, Konopelski P, Ufnal M (2018) Indole and indoxyl sulfate, gut bacteria metabolites of tryptophan, change arterial blood pressure via peripheral and central mechanisms in rats. Pharmacol Res 130:172\u2013179. https:\/\/doi.org\/10.1016\/j.phrs.2017.12.025","journal-title":"Pharmacol Res"},{"key":"2289_CR136","doi-asserted-by":"publisher","unstructured":"Sun CY, Chang SC, Wu MS (2012) Uremic toxins induce kidney fibrosis by activating intrarenal renin-angiotensin-aldosterone system associated epithelial-to-mesenchymal transition. PLoS One 7:e34026. https:\/\/doi.org\/10.1371\/journal.pone.0034026","DOI":"10.1371\/journal.pone.0034026"},{"key":"2289_CR137","doi-asserted-by":"publisher","unstructured":"Sun CY, Li JR, Wang YY, Lin SY, Ou YC, Lin CJ, Wang JD, Liao SL, Chen CJ (2021) Indoxyl sulfate caused behavioral abnormality and neurodegeneration in mice with unilateral nephrectomy. Aging (Albany NY) 13:6681\u20136701. https:\/\/doi.org\/10.18632\/aging.202523","DOI":"10.18632\/aging.202523"},{"key":"2289_CR138","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3389\/fendo.2020.00025","volume":"11","author":"YP Silva","year":"2020","unstructured":"Silva YP, Bernardi A, Frozza RL (2020) The role of short-chain fatty acids from gut microbiota in gut-brain communication. Front Endocrinol (Lausanne) 11:25. https:\/\/doi.org\/10.3389\/fendo.2020.00025","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2289_CR139","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s40168-018-0439-y","volume":"6","author":"L Hoyles","year":"2018","unstructured":"Hoyles L, Snelling T, Umlai UK, Nicholson JK, Carding SR, Glen RC, McArthur S (2018) Microbiome-host systems interactions: protective effects of propionate upon the blood-brain barrier. Microbiome 6:55. https:\/\/doi.org\/10.1186\/s40168-018-0439-y","journal-title":"Microbiome"},{"key":"2289_CR140","doi-asserted-by":"publisher","first-page":"154","DOI":"10.3390\/biomedicines8060154","volume":"8","author":"SP Mishra","year":"2020","unstructured":"Mishra SP, Karunakar P, Taraphder S, Yadav H (2020) Free fatty acid receptors 2 and 3 as microbial metabolite sensors to shape host health: pharmacophysiological view. Biomedicines 8:154. https:\/\/doi.org\/10.3390\/biomedicines8060154","journal-title":"Biomedicines"},{"key":"2289_CR141","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/(sici)1099-0461(2000)14:1<1::aid-jbt1>3.0.co;2-4","volume":"14","author":"PM Garrison","year":"2000","unstructured":"Garrison PM, Denison MS (2000) Analysis of the murine AhR gene promoter. J Biochem Mol Toxicol 14:1\u201310. https:\/\/doi.org\/10.1002\/(sici)1099-0461(2000)14:1%3c1::aid-jbt1%3e3.0.co;2-4","journal-title":"J Biochem Mol Toxicol"},{"key":"2289_CR142","doi-asserted-by":"publisher","first-page":"2105637","DOI":"10.1080\/19490976.2022.2105637","volume":"14","author":"M Modoux","year":"2022","unstructured":"Modoux M, Rolhion N, Lefevre JH, Oeuvray C, Nadvorn\u00edk P, Illes P, Emond P, Parc Y, Mani S, Dvorak Z et al (2022) Butyrate acts through HDAC inhibition to enhance aryl hydrocarbon receptor activation by gut microbiota-derived ligands. Gut Microbes 14:2105637. https:\/\/doi.org\/10.1080\/19490976.2022.2105637","journal-title":"Gut Microbes"},{"key":"2289_CR143","doi-asserted-by":"publisher","first-page":"16014","DOI":"10.1038\/npjbiofilms.2016.14","volume":"2","author":"A Korecka","year":"2016","unstructured":"Korecka A, Dona A, Lahiri S, Tett AJ, Al-Asmakh M, Braniste V, D\u2019Arienzo R, Abbaspour A, Reichardt N, Fujii-Kuriyama Y et al (2016) Bidirectional communication between the aryl hydrocarbon receptor (AhR) and the microbiome tunes host metabolism. NPJ Biofilms Microbiomes 2:16014. https:\/\/doi.org\/10.1038\/npjbiofilms.2016.14","journal-title":"NPJ Biofilms Microbiomes"},{"key":"2289_CR144","doi-asserted-by":"publisher","first-page":"10163","DOI":"10.1038\/s41598-017-10824-x","volume":"7","author":"UH Jin","year":"2017","unstructured":"Jin UH, Cheng Y, Park H, Davidson LA, Callaway ES, Chapkin RS, Jayaraman A, Asante A, Allred C, Weaver EA et al (2017) Short chain fatty acids enhance aryl hydrocarbon (Ah) responsiveness in mouse colonocytes and caco-2 human colon cancer cells. Sci Rep 7:10163. https:\/\/doi.org\/10.1038\/s41598-017-10824-x","journal-title":"Sci Rep"},{"key":"2289_CR145","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1038\/sj.bjp.0705682","volume":"141","author":"J Huuskonen","year":"2004","unstructured":"Huuskonen J, Suuronen T, Nuutinen T, Kyrylenko S, Salminen A (2004) Regulation of microglial inflammatory response by sodium butyrate and short-chain fatty acids. Br J Pharmacol 141:874\u2013880. https:\/\/doi.org\/10.1038\/sj.bjp.0705682","journal-title":"Br J Pharmacol"},{"key":"2289_CR146","doi-asserted-by":"publisher","unstructured":"Jiang Y, Li K, Li X, Xu L, Yang Z (2021) Sodium butyrate ameliorates the impairment of synaptic plasticity by inhibiting the neuroinflammation in 5XFAD mice. Chem Biol Interact 341:109452. https:\/\/doi.org\/10.1016\/j.cbi.2021.109452","DOI":"10.1016\/j.cbi.2021.109452"},{"key":"2289_CR147","doi-asserted-by":"publisher","first-page":"91","DOI":"10.3233\/JAD-190120","volume":"74","author":"WMADB Fernando","year":"2020","unstructured":"Fernando WMADB, Martins IJ, Morici M, Bharadwaj P, Rainey-Smith SR, Lim WLF, Martins RN (2020) Sodium butyrate reduces brain amyloid-\u03b2 levels and improves cognitive memory performance in an Alzheimer\u2019s disease transgenic mouse model at an early disease stage. J Alzheimers Dis 74:91\u201399. https:\/\/doi.org\/10.3233\/JAD-190120","journal-title":"J Alzheimers Dis"},{"key":"2289_CR148","doi-asserted-by":"publisher","unstructured":"Colombo AV, Sadler RK, Llovera G, Singh V, Roth S, Heindl S, Sebastian Monasor L, Verhoeven A, Peters F, Parhizkar S et al (2021) Microbiota-derived short chain fatty acids modulate microglia and promote A\u03b2 plaque deposition. Elife 10:e59826. https:\/\/doi.org\/10.7554\/eLife.59826","DOI":"10.7554\/eLife.59826"},{"key":"2289_CR149","doi-asserted-by":"publisher","first-page":"683","DOI":"10.3233\/JAD-200306","volume":"78","author":"M Marizzoni","year":"2020","unstructured":"Marizzoni M, Cattaneo A, Mirabelli P, Festari C, Lopizzo N, Nicolosi V, Mombelli E, Mazzelli M, Luongo D, Naviglio D et al (2020) Short-chain fatty acids and lipopolysaccharide as mediators between gut dysbiosis and amyloid pathology in Alzheimer\u2019s disease. J Alzheimers Dis 78:683\u2013697. https:\/\/doi.org\/10.3233\/JAD-200306","journal-title":"J Alzheimers Dis"},{"key":"2289_CR150","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/s12987-020-00230-3","volume":"17","author":"H Kadry","year":"2020","unstructured":"Kadry H, Noorani B, Cucullo L (2020) A blood-brain barrier overview on structure, function, impairment, and biomarkers of integrity. Fluids Barriers CNS 17:69. https:\/\/doi.org\/10.1186\/s12987-020-00230-3","journal-title":"Fluids Barriers CNS"},{"key":"2289_CR151","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1038\/nrn.2017.48","volume":"18","author":"K Kisler","year":"2017","unstructured":"Kisler K, Nelson AR, Montagne A, Zlokovic BV (2017) Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease. Nat Rev Neurosci 18:419\u2013434. https:\/\/doi.org\/10.1038\/nrn.2017.48","journal-title":"Nat Rev Neurosci"},{"key":"2289_CR152","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.neuro.2003.08.007","volume":"25","author":"CR Filbrandt","year":"2004","unstructured":"Filbrandt CR, Wu Z, Zlokovic B, Opanashuk L, Gasiewicz TA (2004) Presence and functional activity of the aryl hydrocarbon receptor in isolated murine cerebral vascular endothelial cells and astrocytes. Neurotoxicology 25:605\u2013616. https:\/\/doi.org\/10.1016\/j.neuro.2003.08.007","journal-title":"Neurotoxicology"},{"key":"2289_CR153","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1096\/fj.10-169227","volume":"25","author":"X Wang","year":"2011","unstructured":"Wang X, Hawkins BT, Miller DS (2011) Aryl hydrocarbon receptor-mediated up-regulation of ATP-driven xenobiotic efflux transporters at the blood-brain barrier. FASEB J 25:644\u2013652. https:\/\/doi.org\/10.1096\/fj.10-169227","journal-title":"FASEB J"},{"key":"2289_CR154","doi-asserted-by":"publisher","first-page":"941","DOI":"10.3109\/00498254.2014.919430","volume":"44","author":"H Liu","year":"2014","unstructured":"Liu H, Li Y, Lu S, Wu Y, Sahi J (2014) Temporal expression of transporters and receptors in a rat primary co-culture blood-brain barrier model. Xenobiotica 44:941\u2013951. https:\/\/doi.org\/10.3109\/00498254.2014.919430","journal-title":"Xenobiotica"},{"key":"2289_CR155","doi-asserted-by":"publisher","unstructured":"Ren R, Lu Q, Sherchan P, Fang Y, Lenahan C, Tang L, Huang Y, Liu R, Zhang JH, Zhang J et al (2021) Inhibition of aryl hydrocarbon receptor attenuates hyperglycemia-induced hematoma expansion in an intracerebral hemorrhage mouse model. J Am Heart Assoc 10:e022701. https:\/\/doi.org\/10.1161\/JAHA.121.022701","DOI":"10.1161\/JAHA.121.022701"},{"key":"2289_CR156","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1038\/s44161-021-00014-4","volume":"1","author":"G Barisano","year":"2022","unstructured":"Barisano G, Montagne A, Kisler K, Schneider JA, Wardlaw JM, Zlokovic BV (2022) Blood-brain barrier link to human cognitive impairment and Alzheimer\u2019s disease. Nat Cardiovasc Res 1:108\u2013115. https:\/\/doi.org\/10.1038\/s44161-021-00014-4","journal-title":"Nat Cardiovasc Res"},{"key":"2289_CR157","doi-asserted-by":"publisher","first-page":"404","DOI":"10.3390\/toxins10100404","volume":"10","author":"RAP Maciel","year":"2018","unstructured":"Maciel RAP, Cunha RS, Busato V, Franco CRC, Gregorio PC, Dolenga CJR, Nakao LS, Massy ZA, Boullier A, Pecoits-Filho R et al (2018) Uremia impacts VE-cadherin and ZO-1 expression in human endothelial cell-to-cell junctions. Toxins (Basel) 10:404. https:\/\/doi.org\/10.3390\/toxins10100404","journal-title":"Toxins (Basel)"},{"key":"2289_CR158","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1111\/j.1582-4934.2009.00999.x","volume":"14","author":"MO Romanitan","year":"2010","unstructured":"Romanitan MO, Popescu BO, Spulber S, Bajenaru O, Popescu LM, Winblad B, Bogdanovic N (2010) Altered expression of claudin family proteins in Alzheimer\u2019s disease and vascular dementia brains. J Cell Mol Med 14:1088\u20131100. https:\/\/doi.org\/10.1111\/j.1582-4934.2009.00999.x","journal-title":"J Cell Mol Med"},{"key":"2289_CR159","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.ajpath.2012.03.032","volume":"181","author":"CC Chang","year":"2012","unstructured":"Chang CC, Lee PS, Chou Y, Hwang LL, Juan SH (2012) Mediating effects of aryl-hydrocarbon receptor and RhoA in altering brain vascular integrity: the therapeutic potential of statins. Am J Pathol 181:211\u2013221. https:\/\/doi.org\/10.1016\/j.ajpath.2012.03.032","journal-title":"Am J Pathol"},{"key":"2289_CR160","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1111\/jon.12264","volume":"26","author":"S Verclytte","year":"2016","unstructured":"Verclytte S, Lopes R, Lenfant P, Rollin A, Semah F, Leclerc X, Pasquier F, Delmaire C (2016) Cerebral hypoperfusion and hypometabolism detected by arterial spin labeling MRI and FDG-PET in early-onset Alzheimer\u2019s disease. J Neuroimaging 26:207\u2013212. https:\/\/doi.org\/10.1111\/jon.12264","journal-title":"J Neuroimaging"},{"key":"2289_CR161","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1016\/j.jalz.2017.02.007","volume":"13","author":"RB Nielsen","year":"2017","unstructured":"Nielsen RB, Egefjord L, Angleys H, Mouridsen K, Gejl M, M\u00f6ller A, Brock B, Braendgaard H, Gottrup H, Rungby J et al (2017) Capillary dysfunction is associated with symptom severity and neurodegeneration in Alzheimer\u2019s disease. Alzheimers Dement 13:1143\u20131153. https:\/\/doi.org\/10.1016\/j.jalz.2017.02.007","journal-title":"Alzheimers Dement"},{"key":"2289_CR162","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1007\/s12012-008-9027-x","volume":"8","author":"PG Kopf","year":"2008","unstructured":"Kopf PG, Huwe JK, Walker MK (2008) Hypertension, cardiac hypertrophy, and impaired vascular relaxation induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin are associated with increased superoxide. Cardiovasc Toxicol 8:181\u2013193. https:\/\/doi.org\/10.1007\/s12012-008-9027-x","journal-title":"Cardiovasc Toxicol"},{"key":"2289_CR163","doi-asserted-by":"publisher","unstructured":"Coelho NR, Matos C, Pimpao AB, Correia MJ, Sequeira CO, Morello J, Pereira SA, Monteiro EC (2021) AHR canonical pathway: in vivo findings to support novel antihypertensive strategies. Pharmacol Res 165:105407. https:\/\/doi.org\/10.1016\/j.phrs.2020.105407","DOI":"10.1016\/j.phrs.2020.105407"},{"key":"2289_CR164","doi-asserted-by":"publisher","first-page":"3939","DOI":"10.2174\/1381612827666210706161733","volume":"27","author":"YN Kwon","year":"2021","unstructured":"Kwon YN, Kim YJ (2021) Gut-brain-microbiota axis and hypertension: a literature review. Curr Pharm Des 27:3939\u20133946. https:\/\/doi.org\/10.2174\/1381612827666210706161733","journal-title":"Curr Pharm Des"},{"key":"2289_CR165","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1161\/CIRCRESAHA.116.303587","volume":"116","author":"L Te Riet","year":"2015","unstructured":"Te Riet L, van Esch JH, Roks AJ, van den Meiracker AH, Danser AH (2015) Hypertension: renin-angiotensin-aldosterone system alterations. Circ Res 116:960\u2013975. https:\/\/doi.org\/10.1161\/CIRCRESAHA.116.303587","journal-title":"Circ Res"},{"key":"2289_CR166","doi-asserted-by":"publisher","first-page":"G355","DOI":"10.1152\/ajpgi.00099.2021","volume":"321","author":"K Jaworska","year":"2021","unstructured":"Jaworska K, Koper M, Ufnal M (2021) Gut microbiota and renin-angiotensin system: a complex interplay at local and systemic levels. Am J Physiol Gastrointest Liver Physiol 321:G355\u2013G366. https:\/\/doi.org\/10.1152\/ajpgi.00099.2021","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"2289_CR167","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s11906-019-1011-2","volume":"22","author":"P Nakagawa","year":"2020","unstructured":"Nakagawa P, Gomez J, Grobe JL, Sigmund CD (2020) The renin-angiotensin system in the central nervous system and its role in blood pressure regulation. Curr Hypertens Rep 22:7. https:\/\/doi.org\/10.1007\/s11906-019-1011-2","journal-title":"Curr Hypertens Rep"},{"key":"2289_CR168","doi-asserted-by":"publisher","first-page":"C685","DOI":"10.1152\/ajpcell.00236.2012","volume":"304","author":"H Shimizu","year":"2013","unstructured":"Shimizu H, Saito S, Higashiyama Y, Nishijima F, Niwa T (2013) CREB, NF-\u03baB, and NADPH oxidase coordinately upregulate indoxyl sulfate-induced angiotensinogen expression in proximal tubular cells. Am J Physiol Cell Physiol 304:C685\u2013C692. https:\/\/doi.org\/10.1152\/ajpcell.00236.2012","journal-title":"Am J Physiol Cell Physiol"},{"key":"2289_CR169","first-page":"567","volume":"267","author":"F Qadri","year":"1993","unstructured":"Qadri F, Culman J, Veltmar A, Maas K, Rascher W, Unger T (1993) Angiotensin II-induced vasopressin release is mediated through \u03b11 adrenoceptors and angiotensin II AT1 receptors in the supraoptic nucleus. J Pharmacol Exp Ther 267:567\u2013574","journal-title":"J Pharmacol Exp Ther"},{"key":"2289_CR170","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1111\/j.1549-8719.2010.00060.x","volume":"17","author":"SA Vital","year":"2010","unstructured":"Vital SA, Terao S, Nagai M, Granger DN (2010) Mechanisms underlying the cerebral microvascular responses to angiotensin II-induced hypertension. Microcirculation 17:641\u2013649. https:\/\/doi.org\/10.1111\/j.1549-8719.2010.00060.x","journal-title":"Microcirculation"},{"key":"2289_CR171","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1007\/s12012-022-09730-0","volume":"22","author":"H Wu","year":"2022","unstructured":"Wu H, Sun Q, Yuan S, Wang J, Li F, Gao H, Chen X, Yang R, Xu J (2022) AT1 receptors: their actions from hypertension to cognitive impairment. Cardiovasc Toxicol 22:311\u2013325. https:\/\/doi.org\/10.1007\/s12012-022-09730-0","journal-title":"Cardiovasc Toxicol"},{"key":"2289_CR172","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1016\/j.neuroscience.2010.09.029","volume":"171","author":"M Zhang","year":"2010","unstructured":"Zhang M, Mao Y, Ramirez SH, Tuma RF, Chabrashvili T (2010) Angiotensin II induced cerebral microvascular inflammation and increased blood-brain barrier permeability via oxidative stress. Neuroscience 171:852\u2013858. https:\/\/doi.org\/10.1016\/j.neuroscience.2010.09.029","journal-title":"Neuroscience"},{"key":"2289_CR173","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/j.bcp.2011.06.011","volume":"82","author":"LN Agbor","year":"2011","unstructured":"Agbor LN, Elased KM, Walker MK (2011) Endothelial cell-specific aryl hydrocarbon receptor knockout mice exhibit hypotension mediated, in part, by an attenuated angiotensin II responsiveness. Biochem Pharmacol 82:514\u2013523. https:\/\/doi.org\/10.1016\/j.bcp.2011.06.011","journal-title":"Biochem Pharmacol"},{"key":"2289_CR174","doi-asserted-by":"publisher","first-page":"1599","DOI":"10.1016\/j.toxrep.2021.08.009","volume":"8","author":"G Romero Caimi","year":"2021","unstructured":"Romero Caimi G, Gorzalczany S, Bonazzola P, Deza Z, Roson MI, Alvarez L, Castilla R (2021) Angiotensin II type 1 receptor is involved in hypertension and vascular alterations caused by environmental toxicant hexachlorobenzene. Toxicol Rep 8:1599\u20131606. https:\/\/doi.org\/10.1016\/j.toxrep.2021.08.009","journal-title":"Toxicol Rep"},{"key":"2289_CR175","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1139\/cjpp-2017-0640","volume":"96","author":"B Ongali","year":"2018","unstructured":"Ongali B, Nicolakakis N, Tong XK, Lecrux C, Imboden H, Hamel E (2018) Transforming growth factor-\u03b21 induces cerebrovascular dysfunction and astrogliosis through angiotensin II type 1 receptor-mediated signaling pathways. Can J Physiol Pharmacol 96:527\u2013534. https:\/\/doi.org\/10.1139\/cjpp-2017-0640","journal-title":"Can J Physiol Pharmacol"},{"key":"2289_CR176","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/s0002-9440(10)64713-x","volume":"156","author":"T Wyss-Coray","year":"2000","unstructured":"Wyss-Coray T, Lin C, Sanan DA, Mucke L, Masliah E (2000) Chronic overproduction of transforming growth factor-\u03b21 by astrocytes promotes Alzheimer\u2019s disease-like microvascular degeneration in transgenic mice. Am J Pathol 156:139\u2013150. https:\/\/doi.org\/10.1016\/s0002-9440(10)64713-x","journal-title":"Am J Pathol"},{"key":"2289_CR177","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.3233\/JAD-215051","volume":"84","author":"S Ismael","year":"2021","unstructured":"Ismael S, Mirzahosseini G, Ahmed HA, Yoo A, Kassan M, Malik KU, Ishrat T (2021) Renin-angiotensin system alterations in the human Alzheimer\u2019s disease brain. J Alzheimers Dis 84:1473\u20131484. https:\/\/doi.org\/10.3233\/JAD-215051","journal-title":"J Alzheimers Dis"},{"key":"2289_CR178","doi-asserted-by":"publisher","first-page":"129","DOI":"10.3389\/fnagi.2017.00129","volume":"9","author":"JL Labandeira-Garcia","year":"2017","unstructured":"Labandeira-Garcia JL, Rodr\u00edguez-Perez AI, Garrido-Gil P, Rodriguez-Pallares J, Lanciego JL, Guerra MJ (2017) Brain renin-angiotensin system and microglial polarization: implications for aging and neurodegeneration. Front Aging Neurosci 9:129. https:\/\/doi.org\/10.3389\/fnagi.2017.00129","journal-title":"Front Aging Neurosci"},{"key":"2289_CR179","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1186\/s13041-016-0211-9","volume":"9","author":"J Zhu","year":"2016","unstructured":"Zhu J, Song W, Li L, Fan X (2016) Endothelial nitric oxide synthase: a potential therapeutic target for cerebrovascular diseases. Mol Brain 9:30. https:\/\/doi.org\/10.1186\/s13041-016-0211-9","journal-title":"Mol Brain"},{"key":"2289_CR180","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1002\/jcp.25497","volume":"232","author":"CC Chang","year":"2017","unstructured":"Chang CC, Hsu YH, Chou HC, Lee YG, Juan SH (2017) 3-Methylcholanthrene\/aryl-hydrocarbon receptor-mediated hypertension through eNOS inactivation. J Cell Physiol 232:1020\u20131029. https:\/\/doi.org\/10.1002\/jcp.25497","journal-title":"J Cell Physiol"},{"key":"2289_CR181","doi-asserted-by":"publisher","first-page":"5839","DOI":"10.1073\/pnas.1804932115","volume":"115","author":"R Radi","year":"2018","unstructured":"Radi R (2018) Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine. Proc Natl Acad Sci USA 115:5839\u20135848. https:\/\/doi.org\/10.1073\/pnas.1804932115","journal-title":"Proc Natl Acad Sci USA"},{"key":"2289_CR182","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1124\/mol.112.083303","volume":"83","author":"T Wada","year":"2013","unstructured":"Wada T, Sunaga H, Ohkawara R, Shimba S (2013) Aryl hydrocarbon receptor modulates NADPH oxidase activity via direct transcriptional regulation of p40phox expression. Mol Pharmacol 83:1133\u20131140. https:\/\/doi.org\/10.1124\/mol.112.083303","journal-title":"Mol Pharmacol"},{"key":"2289_CR183","doi-asserted-by":"publisher","unstructured":"Nakagawa K, Itoya M, Takemoto N, Matsuura Y, Tawa M, Matsumura Y, Ohkita M (2021) Indoxyl sulfate induces ROS production via the aryl hydrocarbon receptor-NADPH oxidase pathway and inactivates NO in vascular tissues. Life Sci 265:118807. https:\/\/doi.org\/10.1016\/j.lfs.2020.118807","DOI":"10.1016\/j.lfs.2020.118807"},{"key":"2289_CR184","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.1016\/j.bbadis.2018.11.007","volume":"1865","author":"P Picon-Pages","year":"2019","unstructured":"Picon-Pages P, Garcia-Buendia J, Munoz FJ (2019) Functions and dysfunctions of nitric oxide in brain. Biochim Biophys Acta Mol Basis Dis 1865:1949\u20131967. https:\/\/doi.org\/10.1016\/j.bbadis.2018.11.007","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"2289_CR185","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1161\/01.HYP.0000138068.03893.40","volume":"44","author":"IB Wilkinson","year":"2004","unstructured":"Wilkinson IB, Franklin SS, Cockcroft JR (2004) Nitric oxide and the regulation of large artery stiffness: from physiology to pharmacology. Hypertension 44:112\u2013116. https:\/\/doi.org\/10.1161\/01.HYP.0000138068.03893.40","journal-title":"Hypertension"},{"key":"2289_CR186","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.ajpath.2020.10.012","volume":"191","author":"Y Oe","year":"2021","unstructured":"Oe Y, Mitsui S, Sato E, Shibata N, Kisu K, Sekimoto A, Miyazaki M, Sato H, Ito S, Takahashi N (2021) Lack of endothelial nitric oxide synthase accelerates ectopic calcification in uremic mice fed an adenine and high phosphorus diet. Am J Pathol 191:283\u2013293. https:\/\/doi.org\/10.1016\/j.ajpath.2020.10.012","journal-title":"Am J Pathol"},{"key":"2289_CR187","doi-asserted-by":"publisher","first-page":"569","DOI":"10.3233\/JAD-2012-120670","volume":"32","author":"N Toda","year":"2012","unstructured":"Toda N, Okamura T (2012) Cerebral blood flow regulation by nitric oxide in Alzheimer\u2019s disease. J Alzheimers Dis 32:569\u2013578. https:\/\/doi.org\/10.3233\/JAD-2012-120670","journal-title":"J Alzheimers Dis"},{"key":"2289_CR188","doi-asserted-by":"publisher","unstructured":"Liu R, Liu H, Ha Y, Tilton RG, Zhang W (2014) Oxidative stress induces endothelial cell senescence via downregulation of Sirt6. Biomed Res Int 2014:902842. https:\/\/doi.org\/10.1155\/2014\/902842","DOI":"10.1155\/2014\/902842"},{"key":"2289_CR189","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1161\/HYPERTENSIONAHA.117.07802","volume":"70","author":"TJ Guzik","year":"2017","unstructured":"Guzik TJ, Touyz RM (2017) Oxidative stress, inflammation, and vascular aging in hypertension. Hypertension 70:660\u2013667. https:\/\/doi.org\/10.1161\/HYPERTENSIONAHA.117.07802","journal-title":"Hypertension"},{"key":"2289_CR190","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/s0009-2797(02)00067-4","volume":"141","author":"TP Dalton","year":"2002","unstructured":"Dalton TP, Puga A, Shertzer HG (2002) Induction of cellular oxidative stress by aryl hydrocarbon receptor activation. Chem Biol Interact 141:77\u201395. https:\/\/doi.org\/10.1016\/s0009-2797(02)00067-4","journal-title":"Chem Biol Interact"},{"key":"2289_CR191","doi-asserted-by":"publisher","first-page":"3565127","DOI":"10.1155\/2016\/3565127","volume":"2016","author":"P Davalli","year":"2016","unstructured":"Davalli P, Mitic T, Caporali A, Lauriola A, D\u2019Arca D (2016) ROS, cell senescence, and novel molecular mechanisms in aging and age-related diseases. Oxid Med Cell Longev 2016:3565127. https:\/\/doi.org\/10.1155\/2016\/3565127","journal-title":"Oxid Med Cell Longev"},{"key":"2289_CR192","doi-asserted-by":"publisher","first-page":"2216","DOI":"10.1253\/circj.cj-10-0117","volume":"74","author":"N Masai","year":"2010","unstructured":"Masai N, Tatebe J, Yoshino G, Morita T (2010) Indoxyl sulfate stimulates monocyte chemoattractant protein-1 expression in human umbilical vein endothelial cells by inducing oxidative stress through activation of the NADPH oxidase-nuclear factor-\u03baB pathway. Circ J 74:2216\u20132224. https:\/\/doi.org\/10.1253\/circj.cj-10-0117","journal-title":"Circ J"},{"key":"2289_CR193","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.brainresrev.2003.08.001","volume":"43","author":"AA Rensink","year":"2003","unstructured":"Rensink AA, de Waal RM, Kremer B, Verbeek MM (2003) Pathogenesis of cerebral amyloid angiopathy. Brain Res Brain Res Rev 43:207\u2013223. https:\/\/doi.org\/10.1016\/j.brainresrev.2003.08.001","journal-title":"Brain Res Brain Res Rev"},{"key":"2289_CR194","doi-asserted-by":"publisher","unstructured":"Sun R, He T, Pan Y, Katusic ZS (2018) Effects of senescence and angiotensin II on expression and processing of amyloid precursor protein in human cerebral microvascular endothelial cells. Aging (Albany NY) 10:100\u2013114. https:\/\/doi.org\/10.18632\/aging.101362","DOI":"10.18632\/aging.101362"},{"key":"2289_CR195","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.neurobiolaging.2021.07.014","volume":"107","author":"A Ionescu-Tucker","year":"2021","unstructured":"Ionescu-Tucker A, Cotman CW (2021) Emerging roles of oxidative stress in brain aging and Alzheimer\u2019s disease. Neurobiol Aging 107:86\u201395. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2021.07.014","journal-title":"Neurobiol Aging"},{"key":"2289_CR196","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/s0003-9861(02)00339-9","volume":"404","author":"Q Ma","year":"2002","unstructured":"Ma Q (2002) Induction and superinduction of 2,3,7,8-tetrachlorodibenzo-rho-dioxin-inducible poly(ADP-ribose) polymerase: role of the aryl hydrocarbon receptor\/aryl hydrocarbon receptor nuclear translocator transcription activation domains and a labile transcription repressor. Arch Biochem Biophys 404:309\u2013316. https:\/\/doi.org\/10.1016\/s0003-9861(02)00339-9","journal-title":"Arch Biochem Biophys"},{"key":"2289_CR197","doi-asserted-by":"publisher","unstructured":"Wang X, He HJ, Xiong X, Zhou S, Wang WW, Feng L, Han R, Xie CL (2021) NAD+ in Alzheimer\u2019s disease: Molecular mechanisms and systematic therapeutic evidence obtained in vivo. Front Cell Dev Biol 9:668491. https:\/\/doi.org\/10.3389\/fcell.2021.668491","DOI":"10.3389\/fcell.2021.668491"},{"key":"2289_CR198","doi-asserted-by":"publisher","first-page":"5436","DOI":"10.1007\/s12035-018-1448-3","volume":"56","author":"K Czubowicz","year":"2019","unstructured":"Czubowicz K, Jesko H, Wencel P, Lukiw WJ, Strosznajder RP (2019) The role of ceramide and sphingosine-1-phosphate in Alzheimer\u2019s disease and other neurodegenerative disorders. Mol Neurobiol 56:5436\u20135455. https:\/\/doi.org\/10.1007\/s12035-018-1448-3","journal-title":"Mol Neurobiol"},{"key":"2289_CR199","doi-asserted-by":"publisher","first-page":"4341","DOI":"10.1074\/jbc.AC119.011170","volume":"295","author":"S Majumder","year":"2020","unstructured":"Majumder S, Kono M, Lee YT, Byrnes C, Li C, Tuymetova G, Proia RL (2020) A genome-wide CRISPR\/Cas9 screen reveals that the aryl hydrocarbon receptor stimulates sphingolipid levels. J Biol Chem 295:4341\u20134349. https:\/\/doi.org\/10.1074\/jbc.AC119.011170","journal-title":"J Biol Chem"},{"key":"2289_CR200","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1038\/s41423-018-0022-2","volume":"16","author":"HC Wang","year":"2019","unstructured":"Wang HC, Wong TH, Wang LT, Su HH, Yu HY, Wu AH, Lin YC, Chen HL, Suen JL, Hsu SH et al (2019) Aryl hydrocarbon receptor signaling promotes ORMDL3-dependent generation of sphingosine-1-phosphate by inhibiting sphingosine-1-phosphate lyase. Cell Mol Immunol 16:783\u2013790. https:\/\/doi.org\/10.1038\/s41423-018-0022-2","journal-title":"Cell Mol Immunol"},{"key":"2289_CR201","doi-asserted-by":"publisher","first-page":"4081","DOI":"10.1242\/jcs.019265","volume":"120","author":"RA Nixon","year":"2007","unstructured":"Nixon RA (2007) Autophagy, amyloidogenesis and Alzheimer disease. J Cell Sci 120:4081\u20134091. https:\/\/doi.org\/10.1242\/jcs.019265","journal-title":"J Cell Sci"},{"key":"2289_CR202","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.pneurobio.2013.06.002","volume":"106\u2013107","author":"A Salminen","year":"2013","unstructured":"Salminen A, Kaarniranta K, Kauppinen A, Ojala J, Haapasalo A, Soininen H, Hiltunen M (2013) Impaired autophagy and APP processing in Alzheimer\u2019s disease: the potential role of Beclin 1 interactome. Prog Neurobiol 106\u2013107:33\u201354. https:\/\/doi.org\/10.1016\/j.pneurobio.2013.06.002","journal-title":"Prog Neurobiol"},{"key":"2289_CR203","doi-asserted-by":"publisher","first-page":"3048","DOI":"10.1080\/15548627.2020.1851897","volume":"17","author":"Z Yang","year":"2021","unstructured":"Yang Z, Lin P, Chen B, Zhang X, Xiao W, Wu S, Huang C, Feng D, Zhang W, Zhang J (2021) Autophagy alleviates hypoxia-induced blood-brain barrier injury via regulation of CLDN5 (claudin 5). Autophagy 17:3048\u20133067. https:\/\/doi.org\/10.1080\/15548627.2020.1851897","journal-title":"Autophagy"},{"key":"2289_CR204","doi-asserted-by":"publisher","unstructured":"Wan C, Liu J, Nie X, Zhao J, Zhou S, Duan Z, Tang C, Liang L, Xu G (2014) 2, 3, 7, 8-Tetrachlorodibenzo-P-dioxin (TCDD) induces premature senescence in human and rodent neuronal cells via ROS-dependent mechanisms. PLoS One 9:e89811. https:\/\/doi.org\/10.1371\/journal.pone.0089811","DOI":"10.1371\/journal.pone.0089811"},{"key":"2289_CR205","doi-asserted-by":"publisher","first-page":"148","DOI":"10.3389\/fnagi.2020.00148","volume":"12","author":"X Han","year":"2020","unstructured":"Han X, Zhang T, Liu H, Mi Y, Gou X (2020) Astrocyte senescence and Alzheimer\u2019s disease: a review. Front Aging Neurosci 12:148. https:\/\/doi.org\/10.3389\/fnagi.2020.00148","journal-title":"Front Aging Neurosci"},{"key":"2289_CR206","doi-asserted-by":"publisher","first-page":"1866","DOI":"10.1074\/jbc.M113.505578","volume":"289","author":"CF Vogel","year":"2014","unstructured":"Vogel CF, Khan EM, Leung PS, Gershwin ME, Chang WL, Wu D, Haarmann-Stemmann T, Hoffmann A, Denison MS (2014) Cross-talk between aryl hydrocarbon receptor and the inflammatory response: a role for nuclear factor-\u03baB. J Biol Chem 289:1866\u20131875. https:\/\/doi.org\/10.1074\/jbc.M113.505578","journal-title":"J Biol Chem"},{"key":"2289_CR207","doi-asserted-by":"publisher","first-page":"12011","DOI":"10.7150\/thno.51144","volume":"10","author":"X Yang","year":"2020","unstructured":"Yang X, Liu H, Ye T, Duan C, Lv P, Wu X, Liu J, Jiang K, Lu H, Yang H et al (2020) AhR activation attenuates calcium oxalate nephrocalcinosis by diminishing M1 macrophage polarization and promoting M2 macrophage polarization. Theranostics 10:12011\u201312025. https:\/\/doi.org\/10.7150\/thno.51144","journal-title":"Theranostics"},{"key":"2289_CR208","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/nature06880","volume":"453","author":"FJ Quintana","year":"2008","unstructured":"Quintana FJ, Basso AS, Iglesias AH, Korn T, Farez MF, Bettelli E, Caccamo M, Oukka M, Weiner HL (2008) Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor. Nature 453:65\u201371. https:\/\/doi.org\/10.1038\/nature06880","journal-title":"Nature"},{"key":"2289_CR209","doi-asserted-by":"publisher","first-page":"10273","DOI":"10.1073\/pnas.191118298","volume":"98","author":"A Monsonego","year":"2001","unstructured":"Monsonego A, Maron R, Zota V, Selkoe DJ, Weiner HL (2001) Immune hyporesponsiveness to amyloid \u03b2-peptide in amyloid precursor protein transgenic mice: implications for the pathogenesis and treatment of Alzheimer\u2019s disease. Proc Natl Acad Sci USA 98:10273\u201310278. https:\/\/doi.org\/10.1073\/pnas.191118298","journal-title":"Proc Natl Acad Sci USA"},{"key":"2289_CR210","doi-asserted-by":"publisher","unstructured":"Krabbe G, Halle A, Matyash V, Rinnenthal JL, Eom GD, Bernhardt U, Miller KR, Prokop S, Kettenmann H, Heppner FL (2013) Functional impairment of microglia coincides with \u03b2-amyloid deposition in mice with Alzheimer-like pathology. PLoS One 8:e60921. https:\/\/doi.org\/10.1371\/journal.pone.0060921","DOI":"10.1371\/journal.pone.0060921"},{"key":"2289_CR211","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/1750-1326-6-16","volume":"6","author":"P Chakrabarty","year":"2011","unstructured":"Chakrabarty P, Herring A, Ceballos-Diaz C, Das P, Golde TE (2011) Hippocampal expression of murine TNF\u03b1 results in attenuation of amyloid deposition in vivo. Mol Neurodegener 6:16. https:\/\/doi.org\/10.1186\/1750-1326-6-16","journal-title":"Mol Neurodegener"},{"key":"2289_CR212","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1111\/imm.13278","volume":"161","author":"JA Pearson","year":"2020","unstructured":"Pearson JA, Wong FS, Wen L (2020) Crosstalk between circadian rhythms and the microbiota. Immunology 161:278\u2013290. https:\/\/doi.org\/10.1111\/imm.13278","journal-title":"Immunology"},{"key":"2289_CR213","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1038\/s41575-021-00452-2","volume":"18","author":"H Choi","year":"2021","unstructured":"Choi H, Rao MC, Chang EB (2021) Gut microbiota as a transducer of dietary cues to regulate host circadian rhythms and metabolism. Nat Rev Gastroenterol Hepatol 18:679\u2013689. https:\/\/doi.org\/10.1038\/s41575-021-00452-2","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2289_CR214","doi-asserted-by":"publisher","unstructured":"Petrus P, Cervantes M, Samad M, Sato T, Chao A, Sato S, Koronowski KB, Park G, Alam Y, Mejhert N et al (2022) Tryptophan metabolism is a physiological integrator regulating circadian rhythms. Mol Metab 64:101556. https:\/\/doi.org\/10.1016\/j.molmet.2022.101556","DOI":"10.1016\/j.molmet.2022.101556"},{"key":"2289_CR215","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1146\/annurev-neuro-060909-153128","volume":"35","author":"JA Mohawk","year":"2012","unstructured":"Mohawk JA, Green CB, Takahashi JS (2012) Central and peripheral circadian clocks in mammals. Annu Rev Neurosci 35:445\u2013462. https:\/\/doi.org\/10.1146\/annurev-neuro-060909-153128","journal-title":"Annu Rev Neurosci"},{"key":"2289_CR216","doi-asserted-by":"publisher","first-page":"4154","DOI":"10.1016\/j.cell.2021.07.001","volume":"184","author":"JF Brooks 2nd","year":"2021","unstructured":"Brooks JF 2nd, Behrendt CL, Ruhn KA, Lee S, Raj P, Takahashi JS, Hooper LV (2021) The microbiota coordinates diurnal rhythms in innate immunity with the circadian clock. Cell 184:4154-4167.e12. https:\/\/doi.org\/10.1016\/j.cell.2021.07.001","journal-title":"Cell"},{"key":"2289_CR217","doi-asserted-by":"publisher","unstructured":"Cheng WY, Ho YS, Chang RC (2022) Linking circadian rhythms to microbiome-gut-brain axis in aging-associated neurodegenerative diseases. Ageing Res Rev 78:101620. https:\/\/doi.org\/10.1016\/j.arr.2022.101620","DOI":"10.1016\/j.arr.2022.101620"},{"key":"2289_CR218","doi-asserted-by":"publisher","first-page":"1957407","DOI":"10.1080\/19490976.2021.1957407","volume":"13","author":"Y Li","year":"2021","unstructured":"Li Y, Shao L, Mou Y, Zhang Y, Ping Y (2021) Sleep, circadian rhythm and gut microbiota: alterations in Alzheimer\u2019s disease and their potential links in the pathogenesis. Gut Microbes 13:1957407. https:\/\/doi.org\/10.1080\/19490976.2021.1957407","journal-title":"Gut Microbes"},{"key":"2289_CR219","doi-asserted-by":"publisher","first-page":"4411","DOI":"10.1038\/s41467-020-18115-2","volume":"11","author":"LM Hablitz","year":"2020","unstructured":"Hablitz LM, Pla V, Giannetto M, Vinitsky HS, St\u00e6ger FF, Metcalfe T, Nguyen R, Benrais A, Nedergaard M (2020) Circadian control of brain glymphatic and lymphatic fluid flow. Nat Commun 11:4411. https:\/\/doi.org\/10.1038\/s41467-020-18115-2","journal-title":"Nat Commun"},{"key":"2289_CR220","doi-asserted-by":"publisher","first-page":"7698","DOI":"10.1523\/JNEUROSCI.0619-21.2021","volume":"41","author":"LM Hablitz","year":"2021","unstructured":"Hablitz LM, Nedergaard M (2021) The glymphatic system: a novel component of fundamental neurobiology. J Neurosci 41:7698\u20137711. https:\/\/doi.org\/10.1523\/JNEUROSCI.0619-21.2021","journal-title":"J Neurosci"},{"key":"2289_CR221","doi-asserted-by":"publisher","first-page":"2576","DOI":"10.1093\/brain\/awaa179","volume":"143","author":"IF Harrison","year":"2020","unstructured":"Harrison IF, Ismail O, Machhada A, Colgan N, Ohene Y, Nahavandi P, Ahmed Z, Fisher A, Meftah S, Murray TK, Ottersen OP, Nagelhus EA, O\u2019Neill MJ, Wells JA, Lythgoe MF (2020) Impaired glymphatic function and clearance of tau in an Alzheimer\u2019s disease model. Brain 143:2576\u20132593. https:\/\/doi.org\/10.1093\/brain\/awaa179","journal-title":"Brain"},{"key":"2289_CR222","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s42466-021-00102-7","volume":"3","author":"I Silva","year":"2021","unstructured":"Silva I, Silva J, Ferreira R, Trigo D (2021) Glymphatic system, AQP4, and their implications in Alzheimer\u2019s disease. Neurol Res Pract 3:5. https:\/\/doi.org\/10.1186\/s42466-021-00102-7","journal-title":"Neurol Res Pract"},{"key":"2289_CR223","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1111\/ejn.14361","volume":"51","author":"SA Tischkau","year":"2020","unstructured":"Tischkau SA (2020) Mechanisms of circadian clock interactions with aryl hydrocarbon receptor signalling. Eur J Neurosci 51:379\u2013395. https:\/\/doi.org\/10.1111\/ejn.14361","journal-title":"Eur J Neurosci"},{"key":"2289_CR224","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1093\/toxsci\/kfq022","volume":"115","author":"CX Xu","year":"2010","unstructured":"Xu CX, Krager SL, Liao DF, Tischkau SA (2010) Disruption of CLOCK-BMAL1 transcriptional activity is responsible for aryl hydrocarbon receptor-mediated regulation of Period1 gene. Toxicol Sci 115:98\u2013108. https:\/\/doi.org\/10.1093\/toxsci\/kfq022","journal-title":"Toxicol Sci"},{"key":"2289_CR225","doi-asserted-by":"publisher","first-page":"6514","DOI":"10.1038\/s41598-019-42760-3","volume":"9","author":"KA Fader","year":"2019","unstructured":"Fader KA, Nault R, Doskey CM, Fling RR, Zacharewski TR (2019) 2,3,7,8-Tetrachlorodibenzo-p-dioxin abolishes circadian regulation of hepatic metabolic activity in mice. Sci Rep 9:6514. https:\/\/doi.org\/10.1038\/s41598-019-42760-3","journal-title":"Sci Rep"},{"key":"2289_CR226","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1016\/j.jalz.2016.10.003","volume":"13","author":"P Cronin","year":"2017","unstructured":"Cronin P, McCarthy MJ, Lim ASP, Salmon DP, Galasko D, Masliah E, De Jager PL, Bennett DA, Desplats P (2017) Circadian alterations during early stages of Alzheimer\u2019s disease are associated with aberrant cycles of DNA methylation in BMAL1. Alzheimers Dement 13:689\u2013700. https:\/\/doi.org\/10.1016\/j.jalz.2016.10.003","journal-title":"Alzheimers Dement"},{"key":"2289_CR227","doi-asserted-by":"publisher","first-page":"10052","DOI":"10.1523\/JNEUROSCI.3639-16.2017","volume":"37","author":"R Nakazato","year":"2017","unstructured":"Nakazato R, Kawabe K, Yamada D, Ikeno S, Mieda M, Shimba S, Hinoi E, Yoneda Y, Takarada T (2017) Disruption of Bmal1 impairs blood-brain barrier integrity via pericyte dysfunction. J Neurosci 37:10052\u201310062. https:\/\/doi.org\/10.1523\/JNEUROSCI.3639-16.2017","journal-title":"J Neurosci"},{"key":"2289_CR228","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1038\/s41467-020-20795-9","volume":"12","author":"SL Zhang","year":"2021","unstructured":"Zhang SL, Lahens NF, Yue Z, Arnold DM, Pakstis PP, Schwarz JE, Sehgal A (2021) A circadian clock regulates efflux by the blood-brain barrier in mice and human cells. Nat Commun 12:617. https:\/\/doi.org\/10.1038\/s41467-020-20795-9","journal-title":"Nat Commun"},{"key":"2289_CR229","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1016\/j.tins.2019.05.001","volume":"42","author":"VA Cuddapah","year":"2019","unstructured":"Cuddapah VA, Zhang SL, Sehgal A (2019) Regulation of the blood-brain barrier by circadian rhythms and sleep. Trends Neurosci 42:500\u2013510. https:\/\/doi.org\/10.1016\/j.tins.2019.05.001","journal-title":"Trends Neurosci"},{"key":"2289_CR230","doi-asserted-by":"publisher","unstructured":"Wu KM, Zhang YR, Huang YY, Dong Q, Tan L, Yu JT (2021) The role of the immune system in Alzheimer\u2019s disease. Ageing Res Rev 70:101409. https:\/\/doi.org\/10.1016\/j.arr.2021.101409","DOI":"10.1016\/j.arr.2021.101409"},{"key":"2289_CR231","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.2174\/1568026620666200514090359","volume":"20","author":"F Leblhuber","year":"2020","unstructured":"Leblhuber F, Steiner K, Geisler S, Fuchs D, Gostner JM (2020) On the possible relevance of bottom-up pathways in the pathogenesis of Alzheimer\u2019s disease. Curr Top Med Chem 20:1415\u20131421. https:\/\/doi.org\/10.2174\/1568026620666200514090359","journal-title":"Curr Top Med Chem"},{"key":"2289_CR232","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1007\/s00508-020-01638-5","volume":"132","author":"F Leblhuber","year":"2020","unstructured":"Leblhuber F, Huemer J, Steiner K, Gostner JM, Fuchs D (2020) Knock-on effect of periodontitis to the pathogenesis of Alzheimer\u2019s disease? Wien Klin Wochenschr 132:493\u2013498. https:\/\/doi.org\/10.1007\/s00508-020-01638-5","journal-title":"Wien Klin Wochenschr"}],"container-title":["Journal of Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-023-02289-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00109-023-02289-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-023-02289-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T04:04:00Z","timestamp":1679544240000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00109-023-02289-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,9]]},"references-count":232,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,3]]}},"alternative-id":["2289"],"URL":"https:\/\/doi.org\/10.1007\/s00109-023-02289-5","relation":{},"ISSN":["0946-2716","1432-1440"],"issn-type":[{"value":"0946-2716","type":"print"},{"value":"1432-1440","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,9]]},"assertion":[{"value":"16 September 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 December 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 January 2023","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 February 2023","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The author declares no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}