{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:44:22Z","timestamp":1790703862701,"version":"4.1.0"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T00:00:00Z","timestamp":1661212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Currently, there are no efficient therapies for Alzheimer\u2019s disease (AD) among the elderly, although it is the most common etiology of dementia among the elderly. Quercetin, which has a variety of therapeutic properties, may pave the way for novel approaches to AD treatment. In the AD patients\u2019 frontal cortex, current study aims to identify the potential mechanisms of quercetin\u2019s pharmacological targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>The pharmacological targets of quercetin have been studied from DrugBank and SwissTarget. In order to distinguish AD-associated genes targeted by quercetin (Q-ADGs), we utilized an integrated intersection of gene expressions of the frontal cortex in combination with transcriptome analysis. To detect cortex-related Q-ADGs and immune-related Q-ADGs, a drug screening database and the immune infiltration analysis was utilized. The Q-ADGs were then linked with the AD severity scores (MMSE scores) to find severity-associated Q-ADGs. In addition, the miRNA-seq datasets were examined to identify severity-associated Q-ADG-miRNAs. Twelve genes, more frequently related to AD by previous studies among all the genes identified in the present study, were subjected to the verification of qRT-PCR in AD cell model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the frontal lobe of AD, 207 Q-ADGs were discovered and found that axonogenesis, glial differentiation, and other biological processes had been enriched. There were 155 immune-related Q-ADGs (e.g., COX2, NOS2, HMGB1) and 65 cortex-related Q-ADGs (e.g., FOXO1, CXCL16, NOTCH3). Sixteen Q-ADGs (e.g., STAT3, RORA, BCL6) and 28 miRNAs (e.g., miR-142-5p, miR-17-5p) were found to be related to MMSE scores. In the qRT-PCR results, six out of twelve genes were significantly regulated by quercetin. DYRK1A, FOXO1, NOS2, NGF, NQO1, and RORA genes were novel target of quercetin in AD. DYRK1A, NOS2, and NQO1 genes targeted by quercetin have benefits in the treatment of AD. However, FOXO1, NGF, and RORA genes targeted by quercetin might have a negative impact on AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The role of quercetin in AD appears to be multifaceted, and it can affect patients\u2019 frontal cortex in a variety of pathways, such as axonogenesis, immune infiltration, and glial cell differentiation. DYRK1A, NOS2, and NQO1 might be potential novel effective drug targets for quercetin in AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2022.902092","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T02:28:10Z","timestamp":1661221690000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Network pharmacology identify intersection genes of quercetin and Alzheimer\u2019s disease as potential therapeutic targets"],"prefix":"10.3389","volume":"14","author":[{"given":"Caihui","family":"Wei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renshi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"827","DOI":"10.3233\/JAD-141731","article-title":"A regulatory role for the insulin- and BDNF-linked RORA in the hippocampus: implications for Alzheimer\u2019s disease.","volume":"44","author":"Acquaah-Mensah","year":"2015","journal-title":"J. Alzheimers Dis."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00162","article-title":"PL201, a reported rhamnoside against Alzheimer\u2019s Disease pathology, alleviates neuroinflammation and stimulates Nrf2 signaling.","volume":"11","author":"An","year":"2020","journal-title":"Front. Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2257","DOI":"10.1001\/jama.286.18.2257","article-title":"A founder mutation in presenilin 1 causing early-onset Alzheimer disease in unrelated caribbean hispanic families.","volume":"286","author":"Athan","year":"2001","journal-title":"JAMA"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1002\/alz.058635","article-title":"Applying a deep learning approach focusing on spatiotemporal features in early diagnosis of Alzheimer\u2019s disease.","volume":"17","author":"Babatope","year":"2021","journal-title":"Alzheimers Dement."},{"key":"B5","doi-asserted-by":"publisher","first-page":"D991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: archive for functional genomics data sets\u2014update.","volume":"41","author":"Barrett","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/S1474-4422(09)70332-1","article-title":"Gamma-secretases: from cell biology to therapeutic strategies.","volume":"9","author":"Bergmans","year":"2010","journal-title":"Lancet Neurol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1111\/acel.12648","article-title":"Dyrk1 inhibition improves Alzheimer\u2019s disease-like pathology.","volume":"16","author":"Branca","year":"2017","journal-title":"Aging Cell"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1186\/s12865-017-0198-8","article-title":"Forkhead-box transcription factor 1 affects the apoptosis of natural regulatory T cells by controlling Aven expression.","volume":"18","author":"Cai","year":"2017","journal-title":"BMC Immunol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/s00401-019-01991-4","article-title":"SORL1 genetic variants and Alzheimer disease risk: a literature review and meta-analysis of sequencing data.","volume":"138","author":"Campion","year":"2019","journal-title":"Acta Neuropathol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"W357","DOI":"10.1093\/nar\/gkz382","article-title":"SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules.","volume":"47","author":"Daina","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1111\/j.1582-4934.2009.00688.x","article-title":"PKR, a cognitive decline biomarker, can regulate translation via two consecutive molecular targets p53 and Redd1 in lymphocytes of AD patients.","volume":"13","author":"Damjanac","year":"2009","journal-title":"J. Cell Mol. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/s1474-4422(02)00188-6","article-title":"Secretases as targets for the treatment of Alzheimer\u2019s disease: the prospects.","volume":"1","author":"Dewachter","year":"2002","journal-title":"Lancet Neurol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s12031-018-1100-8","article-title":"Postmortem brain, cerebrospinal fluid, and blood neurotrophic factor levels in Alzheimer\u2019s Disease: a systematic review and meta-analysis.","volume":"65","author":"Du","year":"2018","journal-title":"J. Mol. Neurosci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1006\/mcne.2001.1016","article-title":"The precursor pro-nerve growth factor is the predominant form of nerve growth factor in brain and is increased in Alzheimer\u2019s disease.","volume":"18","author":"Fahnestock","year":"2001","journal-title":"Mol. Cell Neurosci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2164","DOI":"10.1038\/mt.2010.154","article-title":"Long-term delivery of nerve growth factor by encapsulated cell biodelivery in the G\u00f6ttingen minipig basal forebrain.","volume":"18","author":"Fjord-Larsen","year":"2010","journal-title":"Mol. Ther."},{"key":"B16","doi-asserted-by":"publisher","first-page":"3863","DOI":"10.1096\/fj.15-273656","article-title":"Disruption of the NF-\u03baB\/NLRP3 connection by melatonin requires retinoid-related orphan receptor-\u03b1 and blocks the septic response in mice.","volume":"29","author":"Garc\u00eda","year":"2015","journal-title":"FASEB J."},{"key":"B17","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.nbd.2017.06.010","article-title":"Normalizing the gene dosage of DyRk1A in a mouse model of Down syndrome rescues several Alzheimer\u2019s disease phenotypes.","volume":"106","author":"Garc\u00eda-Cerro","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111847","article-title":"The impact of the phytotherapeutic agent quercetin on expression of genes and activity of signaling pathways.","volume":"141","author":"Ghafouri-Fard","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"B19","doi-asserted-by":"publisher","first-page":"3206","DOI":"10.1093\/hmg\/ddy221","article-title":"Transcriptomic RNAseq drug screen in cerebrocortical cultures: toward novel neurogenetic disease therapies.","volume":"27","author":"Hadwen","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2020.111271","article-title":"Modified magnetic core-shell mesoporous silica nano-formulations with encapsulated quercetin exhibit anti-amyloid and antioxidant activity.","volume":"213","author":"Halevas","year":"2020","journal-title":"J. Inorg. Biochem."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.102010","article-title":"Quercetin hinders microglial activation to alleviate neurotoxicity via the interplay between NLRP3 inflammasome and mitophagy.","volume":"44","author":"Han","year":"2021","journal-title":"Redox Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1007\/s12035-016-9728-2","article-title":"Restrained phosphatidylcholine synthesis in a cellular model of down\u2019s syndrome is associated with the overexpression of DyRk1A.","volume":"54","author":"Hijazi","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2009","DOI":"10.1212\/wnl.54.10.2009","article-title":"Increased CSF levels of nerve growth factor in patients with Alzheimer\u2019s disease.","volume":"54","author":"Hock","year":"2000","journal-title":"Neurology"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/2120453","article-title":"FoxO1 overexpression ameliorates TNF-\u03b1-induced oxidative damage and promotes osteogenesis of human periodontal ligament stem cells via antioxidant defense activation.","volume":"2019","author":"Huang","year":"2019","journal-title":"Stem Cells Int."},{"key":"B25","doi-asserted-by":"publisher","first-page":"663","DOI":"10.2174\/15672050136661602081424568","article-title":"Oral triphenylmethane food dye analog, brilliant blue G, prevents neuronal loss in APPSwDI\/NOS2-\/- mouse model.","volume":"13","author":"Irwin","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.584770","article-title":"Yuan-Hu Zhi tong prescription mitigates tau pathology and alleviates memory deficiency in the preclinical models of Alzheimer\u2019s Disease.","volume":"11","author":"Iyaswamy","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1034\/j.1600-0536.2000.042002085.x","article-title":"Effect of an antioxidant (quercetin) on sodium-lauryl-sulfate-induced skin irritation.","volume":"42","author":"Katsarou","year":"2000","journal-title":"Contact Dermatitis"},{"key":"B28","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1248\/bpb.b16-00825","article-title":"Neprilysin is suppressed by dual-specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A) in down-syndrome-derived fibroblasts.","volume":"40","author":"Kawakubo","year":"2017","journal-title":"Biol. Pharm. Bull."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.05920","article-title":"The kinase DYRK1A reciprocally regulates the differentiation of Th17 and regulatory T cells.","volume":"4","author":"Khor","year":"2015","journal-title":"eLife"},{"key":"B30","doi-asserted-by":"publisher","first-page":"D1102","DOI":"10.1093\/nar\/gky1033","article-title":"PubChem 2019 update: improved access to chemical data.","volume":"47","author":"Kim","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/hmg\/ddl437","article-title":"The DYRK1A gene, encoded in chromosome 21 Down syndrome critical region, bridges between beta-amyloid production and tau phosphorylation in Alzheimer disease.","volume":"16","author":"Kimura","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"B32","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1016\/j.neuron.2011.07.001","article-title":"Nitration of tyrosine 10 critically enhances amyloid \u03b2 aggregation and plaque formation.","volume":"71","author":"Kummer","year":"2011","journal-title":"Neuron"},{"key":"B33","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s11481-011-9339-7","article-title":"Nitric oxide decreases the enzymatic activity of insulin degrading enzyme in APP\/PS1 mice.","volume":"7","author":"Kummer","year":"2012","journal-title":"J. Neuroimmune Pharmacol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.bbrc.2021.07.075","article-title":"Senolytic treatment modulates decidualization in human endometrial stromal cells.","volume":"571","author":"Kusama","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B35","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.cell.2004.12.035","article-title":"Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets.","volume":"120","author":"Lewis","year":"2005","journal-title":"Cell"},{"key":"B36","first-page":"1237","article-title":"Quercetin enrich diet during the early-middle not middle-late stage of Alzheimer\u2019s disease ameliorates cognitive dysfunction.","volume":"10","author":"Lu","year":"2018","journal-title":"Am. J. Transl. Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.biopha.2017.07.142","article-title":"Influence of quercetin, naringenin and berberine on glucose transporters and insulin signalling molecules in brain of streptozotocin-induced diabetic rats.","volume":"94","author":"MS","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106300","article-title":"\u03b2-Lapachone attenuates cognitive impairment and neuroinflammation in beta-amyloid induced mouse model of Alzheimer\u2019s disease.","volume":"81","author":"Mokarizadeh","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1002\/jnr.10139","article-title":"Suppressive effects of ansamycins on inducible nitric oxide synthase expression and the development of experimental autoimmune encephalomyelitis.","volume":"67","author":"Murphy","year":"2002","journal-title":"J. Neurosci. Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1023\/B:JOCI.0000040925.55682.a5","article-title":"Quercetin, a flavonoid phytoestrogen, ameliorates experimental allergic encephalomyelitis by blocking IL-12 signaling through JAK-STAT pathway in T lymphocyte.","volume":"24","author":"Muthian","year":"2004","journal-title":"J. Clin. Immunol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1038\/s41587-019-0114-2","article-title":"Determining cell type abundance and expression from bulk tissues with digital cytometry.","volume":"37","author":"Newman","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"21140","DOI":"10.1073\/pnas.1907595116","article-title":"ROR\u03b1 is crucial for attenuated inflammatory response to maintain intestinal homeostasis.","volume":"116","author":"Oh","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B43","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.2174\/1570159X18666201119153807","article-title":"Cholinesterase inhibitory potential of quercetin towards Alzheimer\u2019s disease - a promising natural molecule or fashion of the day? - A narrowed review.","volume":"19","author":"Orhan","year":"2021","journal-title":"Curr. Neuropharmacol."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101206","article-title":"Nrf2: a dark horse in Alzheimer\u2019s disease treatment.","volume":"64","author":"Osama","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"B45","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.phrs.2010.06.003","article-title":"Quercetin attenuates Monocyte Chemoattractant Protein-1 gene expression in glucose primed aortic endothelial cells through NF-kappaB and AP-1.","volume":"62","author":"Panicker","year":"2010","journal-title":"Pharmacol. Res."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1111\/j.1471-4159.2012.07861.x","article-title":"Phosphorylation of Munc18-1 by DyRk1A regulates its interaction with Syntaxin 1 and X11\u03b1.","volume":"122","author":"Park","year":"2012","journal-title":"J. Neurochem."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.2147\/CIA.S64758","article-title":"FOXO1 locus and acetylcholinesterase inhibitors in elderly patients with Alzheimer\u2019s disease.","volume":"9","author":"Paroni","year":"2014","journal-title":"Clin. Interv. Aging"},{"key":"B48","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/j.ejmech.2018.08.093","article-title":"DYRK1A kinase inhibition with emphasis on neurodegeneration: a comprehensive evolution story-cum-perspective.","volume":"158","author":"Pathak","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"B49","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1080\/10717544.2020.1762262","article-title":"Brain delivery of quercetin-loaded exosomes improved cognitive function in AD mice by inhibiting phosphorylated tau-mediated neurofibrillary tangles.","volume":"27","author":"Qi","year":"2020","journal-title":"Drug Deliv."},{"key":"B50","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/s0009-2797(00)00199-x","article-title":"NAD(P)H:quinone oxidoreductase 1 (NQO1): chemoprotection, bioactivation, gene regulation and genetic polymorphisms.","volume":"129","author":"Ross","year":"2000","journal-title":"Chem. Biol. Interact."},{"key":"B51","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1111\/j.1471-4159.2010.06769.x","article-title":"DyRk1A-mediated phosphorylation of Presenilin 1: a functional link between Down syndrome and Alzheimer\u2019s disease.","volume":"115","author":"Ryu","year":"2010","journal-title":"J. Neurochem."},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1186\/s12950-021-00268-6","article-title":"Anti-inflammatory potential of quercetin in COVID-19 treatment.","volume":"18","author":"Saeedi-Boroujeni","year":"2021","journal-title":"J. Inflamm."},{"key":"B53","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/s0197-4580(03)00117-9","article-title":"Regional NAD(P)H:quinone oxidoreductase activity in Alzheimer\u2019s disease.","volume":"25","author":"SantaCruz","year":"2004","journal-title":"Neurobiol. Aging"},{"key":"B54","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/s0304-3940(01)01694-9","article-title":"Nitric oxide synthase gene polymorphisms in Alzheimer\u2019s disease and dementia with Lewy bodies.","volume":"303","author":"Singleton","year":"2001","journal-title":"Neurosci. Lett."},{"key":"B55","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1021\/cn300094k","article-title":"Recent advances in the design, synthesis, and biological evaluation of selective DYRK1A inhibitors: a new avenue for a disease modifying treatment of Alzheimer\u2019s?","volume":"3","author":"Smith","year":"2012","journal-title":"ACS Chem. Neurosci."},{"key":"B56","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.ejcb.2010.10.010","article-title":"gp130 on macrophages\/granulocytes modulates inflammation during experimental tuberculosis.","volume":"90","author":"Sodenkamp","year":"2011","journal-title":"Eur. J. Cell Biol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.phymed.2018.09.224","article-title":"Curcumin and quercetin synergistically inhibit cancer cell proliferation in multiple cancer cells and modulate Wnt\/\u03b2-catenin signaling and apoptotic pathways in A375 cells.","volume":"52","author":"Srivastava","year":"2019","journal-title":"Phytomedicine"},{"key":"B58","doi-asserted-by":"publisher","first-page":"892","DOI":"10.1016\/j.biopha.2016.10.011","article-title":"Bioactive effects of quercetin in the central nervous system: focusing on the mechanisms of actions.","volume":"84","author":"Suganthy","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"B59","doi-asserted-by":"publisher","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","article-title":"The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene\/measurement sets.","volume":"49","author":"Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"B60","doi-asserted-by":"publisher","first-page":"D204","DOI":"10.1093\/nar\/gku989","article-title":"UniProt: a hub for protein information.","volume":"43","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B61","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.bbr.2014.04.055","article-title":"Neophobia, NQO1 and SIRT1 as premorbid and prodromal indicators of AD in 3xTg-AD mice.","volume":"271","author":"Torres-Lista","year":"2014","journal-title":"Behav. Brain Res."},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21030892","article-title":"Proteomic and genomic changes in tau protein, Which are associated with Alzheimer\u2019s Disease after ischemia-reperfusion brain injury.","volume":"21","author":"U\u0142amek-Kozio\u0142","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B63","doi-asserted-by":"publisher","first-page":"8364","DOI":"10.1007\/s12035-019-01684-9","article-title":"Chronic Dyrk1 Inhibition Delays the Onset of AD-Like Pathology in 3xTg-AD Mice.","volume":"56","author":"Velazquez","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1046\/j.1471-4159.2001.00315.x","article-title":"Nerve growth factor modulates the expression and secretion of beta-amyloid precursor protein through different mechanisms in PC12 cells.","volume":"77","author":"Villa","year":"2001","journal-title":"J. Neurochem."},{"key":"B65","doi-asserted-by":"publisher","first-page":"2462","DOI":"10.3760\/cma.j.cn112137-202000123-00151","article-title":"[Neuroprotective effect of ginsenoside Rb-1 on a rat model of Alzheimer\u2019s disease].","volume":"100","author":"Wang","year":"2020","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.28475","article-title":"Methyl B12 protects PC12 cells against cytotoxicity induced by A\u03b225-35.","author":"Wang","year":"2019","journal-title":"J. Cell Biochem."},{"key":"B67","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pneurobio.2009.01.007","article-title":"Neural cell cycle dysregulation and central nervous system diseases.","volume":"89","author":"Wang","year":"2009","journal-title":"Prog. Neurobiol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.biopsych.2017.07.023","article-title":"A novel MicroRNA-124\/PTPN1 signal pathway mediates synaptic and memory deficits in Alzheimer\u2019s Disease.","volume":"83","author":"Wang","year":"2018","journal-title":"Biol. Psychiatry"},{"key":"B69","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1097\/NEN.0b013e318202bfa1","article-title":"Link between DYRK1A overexpression and several-fold enhancement of neurofibrillary degeneration with 3-repeat tau protein in Down syndrome.","volume":"70","author":"Wegiel","year":"2011","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"B70","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1385\/IR:22:2-3:319","article-title":"Nitric oxide synthase 2 and cyclooxygenase 2 interactions in inflammation.","volume":"22","author":"Weinberg","year":"2000","journal-title":"Immunol. Res."},{"key":"B71","doi-asserted-by":"publisher","first-page":"D1074","DOI":"10.1093\/nar\/gkx1037","article-title":"DrugBank 5.0: a major update to the DrugBank database for 2018.","volume":"46","author":"Wishart","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"B72","doi-asserted-by":"publisher","first-page":"2063","DOI":"10.1093\/brain\/aww117","article-title":"Cyclooxygenase inhibition targets neurons to prevent early behavioural decline in Alzheimer\u2019s disease model mice.","volume":"139","author":"Woodling","year":"2016","journal-title":"Brain"},{"key":"B73","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.ymthe.2003.11.010","article-title":"The effects of rAAV2-mediated NGF gene delivery in adult and aged rats.","volume":"9","author":"Wu","year":"2004","journal-title":"Mol. Ther."},{"key":"B74","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.freeradbiomed.2019.01.003","article-title":"5-(3,4-Difluorophenyl)-3-(6-methylpyridin-3-yl)-1,2,4-oxadiazole (DDO-7263), a novel Nrf2 activator targeting brain tissue, protects against MPTP-induced subacute Parkinson\u2019s disease in mice by inhibiting the NLRP3 inflammasome and protects PC12 cells against oxidative stress.","volume":"134","author":"Xu","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"B75","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters.","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8210578","article-title":"Effect of quercetin on PC12 Alzheimer\u2019s Disease cell model induced by A\u03b2 25-35 and its mechanism based on sirtuin1\/Nrf2\/HO-1 pathway.","volume":"2020","author":"Yu","year":"2020","journal-title":"Biomed. Res. Int."},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2020.135322","article-title":"FoxO1 overexpression reduces A\u03b2 production and tau phosphorylation in vitro.","volume":"738","author":"Zhang","year":"2020","journal-title":"Neurosci. Lett."},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.105058","article-title":"Small RNA modifications in Alzheimer\u2019s disease.","volume":"145","author":"Zhang","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"B79","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1038\/ncb2069","article-title":"Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity.","volume":"12","author":"Zhao","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbab199","article-title":"Quercetin for COVID-19 and DENGUE co-infection: a potential therapeutic strategy of targeting critical host signal pathways triggered by SARS-CoV-2 and DENV.","volume":"22","author":"Zheng","year":"2021","journal-title":"Brief Bioinform."},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2021.112498","article-title":"Role of quercetin on sterigmatocystin-induced oxidative stress-mediated toxicity.","volume":"156","author":"Zingales","year":"2021","journal-title":"Food Chem. Toxicol."}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.902092\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T02:28:17Z","timestamp":1661221697000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.902092\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,23]]},"references-count":81,"alternative-id":["10.3389\/fnagi.2022.902092"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2022.902092","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,23]]},"article-number":"902092"}}