{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:31:49Z","timestamp":1787027509621,"version":"build-2736575974"},"reference-count":108,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,12]],"date-time":"2024-10-12T00:00:00Z","timestamp":1728691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["AR-71789"],"award-info":[{"award-number":["AR-71789"]}]},{"name":"NIH","award":["HL139047"],"award-info":[{"award-number":["HL139047"]}]},{"name":"NIH","award":["DK116591"],"award-info":[{"award-number":["DK116591"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Patients with Alzheimer\u2019s disease and related dementia (ADRD) are faced with a formidable challenge of focal amyloid deposits and cerebral amyloid angiopathy (CAA). The treatment of amyloid deposits in ADRD by targeting only oxidative stress, inflammation and hyperlipidemia has not yielded significant positive clinical outcomes. The chronic high-fat diet (HFD), or gut dysbiosis, is one of the major contributors of ADRD in part by disrupted transport, epigenetic DNMT1 and the folate 1-carbon metabolism (FOCM) cycle, i.e., rhythmic methylation\/de-methylation on DNA, an active part of epigenetic memory during genes turning off and on by the gene writer (DNMT1) and eraser (TET2\/FTO) and the transsulfuration pathway by mitochondrial 3-mercaptopyruvate sulfur transferase (3MST)-producing H2S. The repeat CAG expansion and m6A disorder causes senescence and AD. We aim to target the paradigm-shift pathway of the gut\u2013brain microbiome axis that selectively inhibits amyloid deposits and increases mitochondrial transsulfuration and H2S. We have observed an increase in DNMT1 and decreased FTO levels in the cortex of the brain of AD mice. Interestingly, we also observed that probiotic lactobacillus-producing post-biotic folate and lactone\/ketone effectively prevented FOCM-associated gut dysbiosis and amyloid deposits. The s-adenosine-methionine (SAM) transporter (SLC25A) was increased by hyperhomocysteinemia (HHcy). Thus, we hypothesize that chronic gut dysbiosis induces SLC25A, the gene writer, and HHcy, and decreases the gene eraser, leading to a decrease in SLC7A and mitochondrial transsulfuration H2S production and bioenergetics. Lactobacillus engulfs lipids\/cholesterol and a tri-directional post-biotic, folic acid (an antioxidant and inhibitor of beta amyloid deposits; reduces Hcy levels), and the lactate ketone body (fuel for mitochondria) producer increases SLC7A and H2S (an antioxidant, potent vasodilator and neurotransmitter gas) production and inhibits amyloid deposits. Therefore, it is important to discuss whether lactobacillus downregulates SLC25A and DNMT1 and upregulates TET2\/FTO, inhibiting \u03b2-amyloid deposits by lowering homocysteine. It is also important to discuss whether lactobacillus upregulates SLC7A and inhibits \u03b2-amyloid deposits by increasing the mitochondrial transsulfuration of H2S production.<\/jats:p>","DOI":"10.3390\/antiox13101225","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T04:02:58Z","timestamp":1728878578000},"page":"1225","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Lactobacillus Eats Amyloid Plaque and Post-Biotically Attenuates Senescence Due to Repeat Expansion Disorder and Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"13","author":[{"given":"Suresh C.","family":"Tyagi","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Louisville School of Medicine, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2929","DOI":"10.1002\/jcp.25719","article-title":"Dysbiosis and Disease: Many Unknown Ends, Is It Time to Formulate Guidelines for Dysbiosis Research?","volume":"232","author":"Veeranki","year":"2016","journal-title":"J. Cell. Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1126\/science.165.3890.236.d","article-title":"Pliny\u2019s Pheromonic Abortifacients","volume":"165","author":"McCully","year":"1969","journal-title":"Science"},{"key":"ref_3","first-page":"111","article-title":"Vascular pathology of homocysteinemia: Implications for the pathogenesis of arteriosclerosis","volume":"56","author":"McCully","year":"1969","journal-title":"Am. J. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1007\/s00401-011-0879-y","article-title":"TDP-43 pathological changes in early onset familial and sporadic Alzheimer\u2019s disease, late onset Alzheimer\u2019s disease and Down\u2019s Syndrome: Association with age, hippocampal sclerosis and clinical phenotype","volume":"122","author":"Davidson","year":"2011","journal-title":"Acta Neuropathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1001\/archneurol.2009.277","article-title":"Transactive Response DNA-Binding Protein 43 Burden in Familial Alzheimer Disease and Down Syndrome","volume":"66","author":"Lippa","year":"2009","journal-title":"Arch. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"38544","DOI":"10.1074\/jbc.M504202200","article-title":"A Novel Role for GADD45\u03b2 as a Mediator of MMP-13 Gene Expression during Chondrocyte Terminal Differentiation","volume":"280","author":"Ijiri","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3233\/JAD-215318","article-title":"Protective Effect of Rivaroxaban Against Amyloid Pathology and Neuroinflammation Through Inhibiting PAR-1 and PAR-2 in Alzheimer\u2019s Disease Mice","volume":"86","author":"Bian","year":"2022","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Shirafuji, N., Hamano, T., Yen, S.-H., Kanaan, N.M., Yoshida, H., Hayashi, K., Ikawa, M., Yamamura, O., Kuriyama, M., and Nakamoto, Y. (2018). Homocysteine Increases Tau Phosphorylation, Truncation and Oligomerization. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030891"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.jnutbio.2015.03.009","article-title":"Folic acid administration inhibits amyloid \u03b2-peptide accumulation in APP\/PS1 transgenic mice","volume":"26","author":"Li","year":"2015","journal-title":"J. Nutr. Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"25002","DOI":"10.3390\/ijms161025002","article-title":"Folic Acid Inhibits Amyloid \u03b2-Peptide Production through Modulating DNA Methyltransferase Activity in N2a-APP Cells","volume":"16","author":"Li","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3378","DOI":"10.1021\/acschemneuro.2c00402","article-title":"Multiple Actions of H2S-Releasing Peptides in Human \u03b2-Amyloid Expressing C. elegans","volume":"13","author":"Ali","year":"2022","journal-title":"ACS Chem. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"eadj9052","DOI":"10.1126\/scitranslmed.adj9052","article-title":"Antibody-mediated targeting of human microglial leukocyte Ig-like receptor B4 attenuates amyloid pathology in a mouse model","volume":"16","author":"Hou","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1016\/j.cell.2024.03.014","article-title":"Gut microbiome and metabolome profiling in Framingham heart study reveals cholesterol-metabolizing bacteria","volume":"187","author":"Li","year":"2024","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"10879","DOI":"10.1074\/jbc.M009899200","article-title":"Post-translational Processing of \u03b2-Secretase (\u03b2-Amyloid-converting Enzyme) and Its Ectodomain Shedding","volume":"276","author":"Benjannet","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4211","DOI":"10.1074\/jbc.M006947200","article-title":"Processing of \u03b2-Secretase by Furin and Other Members of the Proprotein Convertase Family","volume":"276","author":"Creemers","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"37712","DOI":"10.1074\/jbc.M005339200","article-title":"A Furin-like Convertase Mediates Propeptide Cleavage of BACE, the Alzheimer\u2019s \u03b2-Secretase","volume":"275","author":"Bennett","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"L301","DOI":"10.1152\/ajplung.00065.2010","article-title":"Functional consequences of the collagen\/elastin switch in vascular remodeling in hyperhomocysteinemic wild-type, eNOS\u2212\/\u2212, and iNOS\u2212\/\u2212 mice","volume":"299","author":"Steed","year":"2010","journal-title":"Am. J. Physiol. Cell. Mol. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lynch, M., Pham, W., Sinclair, B., O\u2019brien, T.J., Law, M., and Vivash, L. (2022). Perivascular spaces as a potential biomarker of Alzheimer\u2019s disease. Front. Neurosci., 16.","DOI":"10.3389\/fnins.2022.1021131"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"E1791","DOI":"10.1212\/WNL.0000000000200989","article-title":"Association of Enlarged Perivascular Spaces with Amyloid Burden and Cognitive Decline in Alzheimer Disease Continuum","volume":"99","author":"Jeong","year":"2022","journal-title":"Neurology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.neurobiolaging.2022.10.014","article-title":"Enlarged perivascular space burden associations with arterial stiffness and cognition","volume":"124","author":"Bown","year":"2023","journal-title":"Neurobiol. Aging"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hayden, M.R., and Tyagi, S.C. (2021). Impaired Folate-Mediated One-Carbon Metabolism in Type 2 Diabetes, Late-Onset Alzheimer\u2019s Disease and Long COVID. Medicina, 58.","DOI":"10.3390\/medicina58010016"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s10571-016-0334-7","article-title":"The Science of Vascular Contributions to Cognitive Impairment and Dementia (VCID): A Framework for Advancing Research Priorities in the Cerebrovascular Biology of Cognitive Decline","volume":"36","author":"Corriveau","year":"2016","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1042\/AN20110018","article-title":"Diverse Inflammatory Responses in Transgenic Mouse Models of Alzheimer\u2019s Disease and the Effect of Immunotherapy on These Responses","volume":"3","author":"Wilcock","year":"2011","journal-title":"ASN Neuro"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s11010-012-1425-5","article-title":"Homocysteine alters cerebral microvascular integrity and causes remodeling by antagonizing GABA-A receptor","volume":"371","author":"Lominadze","year":"2012","journal-title":"Mol. Cell. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"H1206","DOI":"10.1152\/ajpheart.00376.2005","article-title":"Homocysteine causes cerebrovascular leakage in mice","volume":"290","author":"Lominadze","year":"2006","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.neuroscience.2016.11.024","article-title":"Time-course of glial changes in the hyperhomocysteinemia model of vascular cognitive impairment and dementia (VCID)","volume":"341","author":"Sudduth","year":"2017","journal-title":"Neuroscience"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/s41430-021-00983-6","article-title":"Prevalence of hyperhomocysteinemia (HHcy) and its major determinants among hypertensive patients over 35 years of age","volume":"76","author":"Cheng","year":"2021","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.2337\/diacare.23.9.1348","article-title":"Insulin is an independent correlate of plasma homocysteine levels in obese children and adolescents","volume":"23","author":"Gallistl","year":"2000","journal-title":"Diabetes Care"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zhou, S., Chen, J., Cheng, L., Fan, K., Xu, M., Ren, W., Chen, Y., Geng, D., Cheng, H., and Luan, X. (2021). Corrigendum: Age-Dependent Association Between Elevated Homocysteine and Cognitive Impairment in a Post-stroke Population: A Prospective Study. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.736283"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1056\/NEJMoa011613","article-title":"Plasma Homocysteine as a Risk Factor for Dementia and Alzheimer\u2019s Disease","volume":"346","author":"Seshadri","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s12944-021-01524-7","article-title":"Effects of chemerin and homocysteine levels and their associations with oc-currence and development of ischemic cerebrovascular disease","volume":"20","author":"Wang","year":"2021","journal-title":"Lipids Health Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4579","DOI":"10.1016\/j.clnu.2021.05.034","article-title":"Hypohomocysteinemia may increases the risk of dementia and Alzheimer\u2019s disease: A nationwide population-based prospective cohort study","volume":"40","author":"Han","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1056\/NEJM200202143460702","article-title":"Homocysteine and Dementias","volume":"346","author":"Loscalzo","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_34","first-page":"21","article-title":"Hyperhomocysteinemia: Atherothrombosis and neurotoxicity","volume":"49","author":"Fridman","year":"1999","journal-title":"Acta Physiol. Pharmacol. Ther. Latinoam."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0895-7061(99)00180-6","article-title":"What level of plasma homocyst(e)ine should be treated? Effects of vitamin therapy on progression of carotid atherosclerosis in patients with homocyst(e)ine levels above and below 14 \u03bcmol\/L","volume":"13","author":"Hackam","year":"2000","journal-title":"Am. J. Hypertens."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1056\/NEJMoa011364","article-title":"Decreased Rate of Coronary Restenosis after Lowering of Plasma Homocysteine Levels","volume":"345","author":"Schnyder","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1006\/exnr.1994.1213","article-title":"NMDA and Not Non-NMDA Receptor Antagonists Are Protective against Seizures Induced by Homocysteine in Neonatal Rats","volume":"130","year":"1994","journal-title":"Exp. Neurol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/BF01244459","article-title":"Decreased susceptibility to seizures induced by bicuculline after transient bilateral clamping of the carotid arteries in rats","volume":"83","author":"Sieklucka","year":"1991","journal-title":"J. Neural Transm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.placenta.2021.09.012","article-title":"Periconceptional maternal and paternal homocysteine levels and early utero-placental (vascular) growth trajectories: The Rotterdam periconception cohort","volume":"115","author":"Hoek","year":"2021","journal-title":"Placenta"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e57","DOI":"10.1017\/jns.2021.53","article-title":"Cobalamin and folate status in women during early pregnancy in Bhaktapur, Nepal","volume":"10","author":"Schwinger","year":"2021","journal-title":"J. Nutr. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S0007114521002841","article-title":"Folic acid supplementation during pregnancy modulates hepatic methyl metabolism and genes expression profile of neonatal lambs of different litter sizes","volume":"128","author":"Wang","year":"2021","journal-title":"Br. J. Nutr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.cmet.2023.02.017","article-title":"Gut-microbiome-expressed 3\u03b2-hydroxysteroid dehydrogenase degrades estradiol and is linked to depression in premenopausal females","volume":"35","author":"Li","year":"2023","journal-title":"Cell Metab."},{"key":"ref_43","first-page":"e12354","article-title":"Integrative analysis of DNA methylation and gene expression identifies genes associated with biological aging in Alzheimer\u2019s disease","volume":"14","author":"Kim","year":"2022","journal-title":"Alzheimer\u2019s Dementia Diagn. Assess. Dis. Monit."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"197","DOI":"10.7150\/thno.79535","article-title":"Role of primary aging hallmarks in Alzheimer\u2019s disease","volume":"13","author":"Zhao","year":"2023","journal-title":"Theranostics"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ma, X., Kim, J.K., Shin, Y.J., Son, Y.H., Lee, D.Y., Park, H.S., and Kim, D.H. (2023). Alleviation of Cognitive Impairment-like Behaviors, Neuroinflammation, Colitis, and Gut Dysbiosis in 5xFAD Transgenic and Aged Mice by Lactobacillus mucosae and Bifidobacterium longum. Nutrients, 15.","DOI":"10.3390\/nu15153381"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1111\/apm.13339","article-title":"Dynamic distribution of gut microbiota during Alzheimer\u2019s disease progression in a mice model","volume":"131","author":"Zhu","year":"2023","journal-title":"APMIS"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Villodres, J.A., Escamilla, A., Mercado-S\u00e1enz, S., Alba-Tercedor, C., Rodriguez-Perez, L.M., Arranz-Salas, I., Sanchez-Varo, R., and Berm\u00fadez, D. (2023). Microbiome Alterations and Alzheimer\u2019s Disease: Modeling Strategies with Transgenic Mice. Biomedicines, 11.","DOI":"10.3390\/biomedicines11071846"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7317","DOI":"10.1039\/D3FO01257C","article-title":"Microbiota dysbiosis caused by dietetic patterns as a promoter of Alzheimer\u2019s disease through metabolic syndrome mechanisms","volume":"14","author":"Silva","year":"2023","journal-title":"Food Funct."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1021\/acs.jafc.2c05829","article-title":"Methionine-Restricted Diet: A Feasible Strategy Against Chronic or Aging-Related Diseases","volume":"71","author":"Wu","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"12896","DOI":"10.1039\/D2FO03366F","article-title":"Dietary methionine restriction improves gut microbiota composition and prevents cognitive impairment ind-galactose-induced aging mice","volume":"13","author":"Xu","year":"2022","journal-title":"Food Funct."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Xi, Y., Zhang, Y., Zhou, Y., Liu, Q., Chen, X., Liu, X., Grune, T., Shi, L., Hou, M., and Liu, Z. (2023). Effects of methionine intake on cognitive function in mild cognitive impairment patients and APP\/PS1 Alzheimer\u2019s Disease model mice: Role of the cystathionine-\u03b2-synthase\/H2S pathway. Redox Biol., 59.","DOI":"10.1016\/j.redox.2022.102595"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"15225","DOI":"10.1021\/acs.jafc.2c04847","article-title":"Dietary Methionine via Dose-Dependent Inhibition of Short-Chain Fatty Acid Production Capacity Contributed to a Potential Risk of Cognitive Dysfunction in Mice","volume":"70","author":"Yang","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1139\/cjpp-2018-0505","article-title":"Circular RNAs constitute an inherent gene regulatory axis in the mammalian eye and brain","volume":"97","author":"George","year":"2019","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.exer.2018.05.026","article-title":"Circular RNAs profiling in the cystathionine-\u03b2-synthase mutant mouse reveals novel gene targets for hyperhomocysteinemia induced ocular disorders","volume":"174","author":"Singh","year":"2018","journal-title":"Exp. Eye Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s11010-020-03934-0","article-title":"Regulation of the parental gene GRM4 by circGrm4 RNA transcript and glutamate-mediated neurovascular toxicity in eyes","volume":"476","author":"Eyob","year":"2021","journal-title":"Mol. Cell. Biochem."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Scalise, M., Galluccio, M., Console, L., Pochini, L., and Indiveri, C. (2018). The Human SLC7A5 (LAT1): The Intriguing Histidine\/Large Neutral Amino Acid Transporter and Its Relevance to Human Health. Front. Chem., 6.","DOI":"10.3389\/fchem.2018.00243"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"181","DOI":"10.3109\/10641969909068660","article-title":"Homocyst(E)Ine and Heart Disease: Pathophysiology of Extracellular Matrix","volume":"21","author":"Tyagi","year":"1999","journal-title":"Clin. Exp. Hypertens."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.neubiorev.2014.04.007","article-title":"One-carbon metabolism in neurodevelopmental disorders: Using broad-based nutraceutics to treat cognitive deficits in complex spectrum disorders","volume":"46","author":"Schaevitz","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2590","DOI":"10.1002\/jcp.29163","article-title":"Dysbiotic 1-carbon metabolism in cardiac muscle remodeling","volume":"235","author":"George","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1038\/s41467-023-36483-3","article-title":"Methionine adenosyltransferase2A inhibition restores metabolism to improve re-generative capacity and strength of aged skeletal muscle","volume":"14","author":"Rajabian","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_61","first-page":"775","article-title":"The role of hyperuricemia in the development of cognitive changes in the elderly","volume":"35","author":"Kunitskaya","year":"2022","journal-title":"Adv. Gerontol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1038\/s41467-019-09713-w","article-title":"A DNMT3A PWWP mutation leads to methylation of bivalent chromatin and growth retardation in mice","volume":"10","author":"Hanna","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1161\/CIRCULATIONAHA.118.033794","article-title":"FTO-Dependent N6 -Methyladenosine Regulates Cardiac Function During Remodeling and Repair","volume":"139","author":"Mathiyalagan","year":"2019","journal-title":"Circulation"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/0021-9150(94)05481-W","article-title":"Role of blood pressure, uric acid, and hemorheological parameters on plasma homocyst(e)ine concentration","volume":"114","author":"Malinow","year":"1995","journal-title":"Atherosclerosis"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1161\/01.CIR.96.6.1745","article-title":"High Homocysteine Levels Are Independently Related to Isolated Systolic Hypertension in Older Adults","volume":"96","author":"Bostom","year":"1997","journal-title":"Circulation"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1161\/01.RES.54.1.30","article-title":"Antihypertensive effect of the GABA receptor agonist muscimol in spontaneously hypertensive rats. Role of the sympathoadrenal axis","volume":"54","author":"Unger","year":"1984","journal-title":"Circ. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1161\/hyp.38.4.896","article-title":"Overexpression of eNOS in the RVLM Causes Hypotension and Bradycardia Via GABA Release","volume":"38","author":"Kishi","year":"2001","journal-title":"Hypertension"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1139\/y99-102","article-title":"Homocyst(e)ine impairs endocardial endothelial function","volume":"77","author":"Tyagi","year":"1999","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1385\/CBB:43:1:037","article-title":"Homocysteine in Microvascular Endothelial Cell Barrier Permeability","volume":"43","author":"Tyagi","year":"2005","journal-title":"Cell Biochem. Biophys."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12987-023-00410-x","article-title":"Long-term administration of CU06-1004 ameliorates cerebrovascular aging and BBB injury in aging mouse model","volume":"20","author":"Kim","year":"2023","journal-title":"Fluids Barriers CNS"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Cheng, Z., Dai, L., Wu, Y., Cao, Y., Chai, X., Wang, P., Liu, C., Ni, M., Gao, F., and Wang, Q. (2023). Correlation of blood\u2013brain barrier leakage with cerebral small vessel disease including cerebral microbleeds in Alzheimer\u2019s disease. Front. Neurol., 14.","DOI":"10.3389\/fneur.2023.1077860"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Shibly, A.Z., Sheikh, A.M., Michikawa, M., Tabassum, S., Azad, A.K., Zhou, X., Zhang, Y., Yano, S., and Nagai, A. (2022). Analysis of Cerebral Small Vessel Changes in AD Model Mice. Biomedicines, 11.","DOI":"10.3390\/biomedicines11010050"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.cell.2022.12.047","article-title":"Transgenerational inheritance of acquired epigenetic signatures at CpG islands in mice","volume":"186","author":"Takahashi","year":"2023","journal-title":"Cell"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1002\/jcp.25450","article-title":"Browning of White Fat: Novel Insight Into Factors, Mechanisms, and Therapeutics","volume":"232","author":"Jeremic","year":"2016","journal-title":"J. Cell. Physiol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Paul, B.D., and Pieper, A.A. (2023). Protective Roles of Hydrogen Sulfide in Alzheimer\u2019s Disease and Traumatic Brain Injury. Antioxidants, 12.","DOI":"10.3390\/antiox12051095"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Gu, Y., Xiao, X., Pan, R., Zhang, J., Zhao, Y., Dong, Y., and Cui, H. (2021). Lactobacillus plantarum dy-1 fermented barley extraction activates white adipocyte browning in high-fat diet-induced obese rats. J. Food Biochem., 45.","DOI":"10.1111\/jfbc.13680"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1152\/japplphysiol.00497.2022","article-title":"Lactate as a myokine and exerkine: Drivers and signals of physiology and metabolism","volume":"134","author":"Brooks","year":"2023","journal-title":"J. Appl. Physiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1007\/s12602-021-09747-x","article-title":"Protective Effect of Lacticaseibacillus casei CRL 431 Postbiotics on Mitochondrial Function and Oxidative Status in Rats with Aflatoxin B1\u2013Induced Oxidative Stress","volume":"13","author":"Garcia","year":"2021","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1161\/CIRCULATIONAHA.115.017355","article-title":"The Failing Heart Relies on Ketone Bodies as a Fuel","volume":"133","author":"Aubert","year":"2016","journal-title":"Circulation"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1161\/CIRCRESAHA.123.321872","article-title":"Ketones and the Heart: Metabolic Principles and Therapeutic Implications","volume":"132","author":"Matsuura","year":"2023","journal-title":"Circ. Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e13833","DOI":"10.1111\/acel.13833","article-title":"Ketone bodies: A double-edged sword for mammalian life span","volume":"22","author":"Tomita","year":"2023","journal-title":"Aging Cell"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1159\/000490615","article-title":"The Gut Microbiota and Healthy Aging: A Mini-Review","volume":"64","author":"Kim","year":"2018","journal-title":"Gerontology"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Albano, C., Silvetti, T., and Brasca, M. (2020). Screening of lactic acid bacteria producing folate and their potential use as adjunct cultures for cheese bio-enrichment. FEMS Microbiol. Lett., 367.","DOI":"10.1093\/femsle\/fnaa059"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nature23480","article-title":"A randomized synbiotic trial to prevent sepsis among infants in rural India","volume":"548","author":"Panigrahi","year":"2017","journal-title":"Nature"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1177\/1073858417707457","article-title":"Neuronal DNA Methyltransferases: Epigenetic Mediators between Synaptic Activity and Gene Expression?","volume":"24","author":"Bayraktar","year":"2017","journal-title":"Neuroscientist"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Bayraktar, G., and Kreutz, M.R. (2018). The Role of Activity-Dependent DNA Demethylation in the Adult Brain and in Neurological Disorders. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00169"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.neuropharm.2013.07.036","article-title":"Active DNA demethylation in post-mitotic neurons: A reason for optimism","volume":"75","author":"Gavin","year":"2013","journal-title":"Neuropharmacology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"6638","DOI":"10.1080\/21655979.2022.2045838","article-title":"A novel epigenetic marker, Ten-eleven translocation family member 2 (TET2), is identified in the intractable epileptic brain and regulates ATP binding cassette subfamily B member 1 (ABCB1) in the blood\u2013brain barrier","volume":"13","author":"Kong","year":"2022","journal-title":"Bioengineered"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/s41593-021-00999-y","article-title":"Large-scale deep multi-layer analysis of Alzheimer\u2019s disease brain reveals strong proteomic disease-related changes not observed at the RNA level","volume":"25","author":"Johnson","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/978-1-0716-1936-0_3","article-title":"Proteomic Profiling of Cerebrospinal Fluid by 16-Plex TMT-Based Mass Spectrometry","volume":"2420","author":"Dey","year":"2022","journal-title":"Methods Mol. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Erickson, A., Zhou, S., Luo, J., Li, L., Huang, X., Even, Z., Huang, H., Xu, H.-M., Peng, J., and Lu, L. (2021). Genetic architecture of protein expression and its regulation in the mouse brain. BMC Genom., 22.","DOI":"10.1186\/s12864-021-08168-y"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1093\/hmg\/ddab360","article-title":"A partial reduction of Drp1 improves cognitive behavior and enhances mitophagy, autophagy and dendritic spines in a transgenic Tau mouse model of Alzheimer disease","volume":"31","author":"Kandimalla","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Leung, L.Y., Cardiff, K., Yang, X., Wilfred, B.S., Gilsdorf, J., and Shear, D. (2018). Selective Brain Cooling Reduces Motor Deficits Induced by Combined Traumatic Brain Injury, Hypoxemia and Hemorrhagic Shock. Front. Neurol., 9.","DOI":"10.3389\/fneur.2018.00612"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/978-1-4939-1372-5_16","article-title":"Perinatal programming of neurodevelopment: Epigenetic mechanisms and the prenatal shaping of the brain","volume":"10","author":"Desplats","year":"2015","journal-title":"Adv. Neurobiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s00213-006-0477-1","article-title":"ERK-mediated NGF signaling in the rat septo-hippocampal pathway diminishes with age","volume":"188","author":"Williams","year":"2006","journal-title":"Psychopharmacology"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12974-019-1412-9","article-title":"Neuroinflammation and fractalkine signaling in Alzheimer\u2019s disease","volume":"16","author":"Finneran","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"575","DOI":"10.4103\/1673-5374.320986","article-title":"Matrin-3 dysfunction in myopathy and motor neuron degeneration","volume":"17","author":"Pandey","year":"2022","journal-title":"Neural Regen. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s00401-021-02333-z","article-title":"DDX17 is involved in DNA damage repair and modifies FUS toxicity in an RGG-domain dependent manner","volume":"142","author":"Fortuna","year":"2021","journal-title":"Acta Neuropathol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"e67587","DOI":"10.7554\/eLife.67587","article-title":"Traumatic injury compromises nucleocytoplasmic transport and leads to TDP-43 pathology","volume":"10","author":"Anderson","year":"2021","journal-title":"eLife"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Winslow, W., McDonough, I., Tallino, S., Decker, A., Vural, A.S., and Velazquez, R. (2021). IntelliCage Automated Behavioral Phenotyping Reveals Behavior Deficits in the 3xTg-AD Mouse Model of Alzheimer\u2019s Disease Associated With Brain Weight. Front. Aging Neurosci., 13.","DOI":"10.3389\/fnagi.2021.720214"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1186\/s12974-020-01956-5","article-title":"Role of sex and high-fat diet in metabolic and hypothalamic disturbances in the 3xTg-AD mouse model of Alzheimer\u2019s disease","volume":"17","author":"Robison","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/s41586-023-06701-5","article-title":"m1A in CAG repeat RNA binds to TDP-43 and induces neurodegeneration","volume":"623","author":"Sun","year":"2023","journal-title":"Nature"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Nguyen, T.B., Miramontes, R., Chillon-Marinas, C., Maimon, R., Vazquez-Sanchez, S., Lau, A.L., McClure, N.R., England, W.E., Singha, M., and Stocksdale, J.T. (2023). Aberrant splicing in Huntington\u2019s disease via disrupted TDP-43 activity accompanied by altered m6A RNA modification. bioRxiv.","DOI":"10.1101\/2023.10.31.565004"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s12974-022-02419-9","article-title":"A selective inhibitor of the NLRP3 inflammasome as a potential therapeutic approach for neuroprotection in a transgenic mouse model of Huntington\u2019s disease","volume":"19","author":"Chen","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_105","first-page":"215.e9","article-title":"HTT gene intermediate alleles in neurodegeneration: Evidence for association with Alzheimer\u2019s disease","volume":"76","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3233\/JHD-140111","article-title":"The Co-Occurrence of Alzheimer\u2019s Disease and Huntington\u2019s Disease: A Neuropathological Study of 15 Elderly Huntington\u2019s Disease Subjects","volume":"3","author":"Davis","year":"2014","journal-title":"J. Huntington\u2019s Dis."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Moschini, V., Mazzeo, S., Bagnoli, S., Padiglioni, S., Emiliani, F., Giacomucci, G., Morinelli, C., Ingannato, A., Freni, T., and Belloni, L. (2022). CAG Repeats within the Non-pathological Range in the HTT Gene Influence Personality Traits in Patients with Subjective Cognitive Decline: A 13-Year Follow-Up Study. Front. Psychiatry, 13.","DOI":"10.3389\/fpsyt.2022.826135"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/ncpneuro0448","article-title":"Mechanisms of Disease: DNA repair defects and neurological disease","volume":"3","author":"Rao","year":"2007","journal-title":"Nat. Clin. Pract. Neurol."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/10\/1225\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:11:53Z","timestamp":1760112713000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/10\/1225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,12]]},"references-count":108,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2024,10]]}},"alternative-id":["antiox13101225"],"URL":"https:\/\/doi.org\/10.3390\/antiox13101225","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,12]]}}}