{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:08:30Z","timestamp":1790770110745,"version":"4.1.0"},"reference-count":84,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s Disease (AD) is a major health problem worldwide. The lack of efficacy of existing therapies for AD is because of diagnosis at late stages of the disease, limited knowledge of biomarkers, and molecular mechanisms of AD pathology, as well as conventional drugs that are focused on symptomatic rather than mechanistic features of the disease. The connection between epigenetics and AD, however, may be useful for the development of novel therapeutics or diagnostic biomarkers for AD. The aim of this study was to investigate a pathogenic role for epigenetics and other biomarkers in the male APP\/BIN1\/COPS5 triple-transgenic (3xTg) mouse model of AD. In the APP\/BIN1\/COPS5 3xTg-AD mouse hippocampus, sirtuin expression and activity decreased, HDAC3 expression and activity increased, PSEN1 mRNA levels were unchanged, PSEN2 and APOE expression was reduced, and levels of the pro-inflammatory marker IL-6 increased; levels of pro-inflammatory COX-2 and TNF\u03b1 and apoptotic (NOS3) markers increased slightly, but these were non-significant. In fixed mouse-brain slices, immunoreactivity for CD11b and \u03b2-amyloid immunostaining increased. APP\/BIN1\/COPS5 3xTg-AD mice are a suitable model for evaluating epigenetic changes in AD, the discovery of new epigenetic-related biomarkers for AD diagnosis, and new epidrugs for the treatment of this neurodegenerative disease.<\/jats:p>","DOI":"10.3390\/ijms23052446","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T22:54:02Z","timestamp":1645656842000},"page":"2446","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Epigenetic Studies in the Male APP\/BIN1\/COPS5 Triple-Transgenic Mouse Model of Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"23","author":[{"given":"Olaia","family":"Mart\u00ednez-Iglesias","sequence":"first","affiliation":[{"name":"EuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, 15165 Corunna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinogran","family":"Naidoo","sequence":"additional","affiliation":[{"name":"EuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, 15165 Corunna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00e1n","family":"Carrera","sequence":"additional","affiliation":[{"name":"EuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, 15165 Corunna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0554-4037","authenticated-orcid":false,"given":"Ram\u00f3n","family":"Cacabelos","sequence":"additional","affiliation":[{"name":"EuroEspes Biomedical Research Center, International Center of Neuroscience and Genomic Medicine, 15165 Corunna, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1517\/17460441.2016.1141892","article-title":"Can cloud-based tools accelerate Alzheimer\u2019s drug discovery?","volume":"11","author":"Cacabelos","year":"2016","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2020). 2020 Alzheimer\u2019s disease facts and figures. Alzheimer\u2019s Dement., 16, 391\u2013460.","DOI":"10.1002\/alz.12068"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1017\/S1041610211002924","article-title":"Dementia time to death: A systematic literature review on survival time and years of life lost in people with dementia","volume":"24","author":"Brodaty","year":"2012","journal-title":"Int. J. Psychogeriatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41572-021-00269-y","article-title":"Alzheimer Disease","volume":"7","author":"Knopman","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2021). 2021 Alzheimer\u2019s Diseases Facts and Figures. Alzheimer\u2019s Dement., 17, 327\u2013406.","DOI":"10.1002\/alz.12328"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1080\/17460441.2018.1457645","article-title":"Have there been improvements in Alzheimer\u2019s disease drug discovery over the past 5 years?","volume":"13","author":"Cacabelos","year":"2018","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_7","first-page":"1","article-title":"Molecular genetics of Alzheimer\u2019s disease and aging","volume":"27","author":"Cacabelos","year":"2005","journal-title":"Methods Find. Exp. Clin. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.2217\/pgs-2016-0031","article-title":"Pharmacogenetic considerations in the treatment of Alzheimer\u2019s disease","volume":"17","author":"Cacabelos","year":"2016","journal-title":"Pharmacogenomics"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Cacabelos, R., Meyyazhagan, A., Carril, J.C., Cacabelos, P., and Teijido, O. (2018). Pharmacogenetics of vascular risk factors in Alzheimer\u2019s disease. J. Pers. Med., 8.","DOI":"10.3390\/jpm8010003"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1111\/bpa.12405","article-title":"Cerebral perfusion enhancing intervention: A new strategy for the prevention of Alzheimer\u2019s disease","volume":"26","year":"2016","journal-title":"Brain Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.brainres.2010.06.011","article-title":"Characterization of the 3xTg-AD mouse model of Alzheimer\u2019s Disease: Part Behavioral and cognitive changes","volume":"1348","author":"Sterniczuk","year":"2010","journal-title":"Brain Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1038\/cdd.2012.14","article-title":"Pivotal role of the RanBP9-cofilin pathway in Ab-induced apoptosis and neurodegeneratiom","volume":"19","author":"Woo","year":"2012","journal-title":"Cell Death Differ."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"727","DOI":"10.3233\/JAD-131550","article-title":"RanBP9 overexpression down-regulates phospho-cofilin, causes early synaptic deficits and impaired learning, and accelerates accumulation of amyloid plaques in the mouse brain","volume":"39","author":"Palavicini","year":"2014","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.bbr.2012.07.004","article-title":"Cognitive and non-cognitive behaviours in the triple transgeinic mouse model of Alzheimer\u2019s Disease expressing mutated APP, PS1 and MAPT (3xTg-AD)","volume":"234","author":"Filali","year":"2012","journal-title":"Behav. Brain Res."},{"key":"ref_15","first-page":"331","article-title":"Comparative characterization of transgenic mouse models of Alzheimer\u2019s disease","volume":"2","author":"Carrera","year":"2017","journal-title":"J. Genom. Med. Pharmacogenom."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/S1474-4422(09)70262-5","article-title":"Epigenetic mechanisms in neurological diseases: Genes, syndromes, and therapies","volume":"8","author":"Urdinguio","year":"2009","journal-title":"Lancet Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/j.neuron.2013.10.023","article-title":"The emerging field of neuroepigenetics","volume":"80","author":"Sweatt","year":"2013","journal-title":"Neuron"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Cacabelos, R., Tellado, I., and Cacabelos, P. (2019). The epigenetic machinery in the lyfe cycle and pharmacoepigenetics. Pharmacoepigenetics, Elsevier.","DOI":"10.1016\/B978-0-12-813939-4.00001-2"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/mp.2016.242","article-title":"Opening up the DNA methylome of dementia","volume":"22","author":"Esteller","year":"2017","journal-title":"Mol. Psychiatry"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/S1474-4422(16)00065-X","article-title":"Epigenetics of dementia: Understanding the disease as a transformation rather than a state","volume":"15","author":"Maloney","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Martinez-Iglesias, O., Carrera, I., Carril, J.C., Fernadez-Novoa, L., Cacabelos, N., and Cacabelos, R. (2020). DNA methylation in Neurodegenerative and Cerebrovascular Disorders. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062220"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/hdy.2010.54","article-title":"Epigenetics and gene expression","volume":"105","author":"Gibney","year":"2010","journal-title":"Heredity"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.pharmthera.2013.03.010","article-title":"Epigenetics: A novel therapeutic approach for the treatment of Alzheimer\u2019s disease","volume":"139","author":"Adwan","year":"2013","journal-title":"Pharmacol. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Teijido, O., and Cacabelos, R. (2018). Pharmacoepigenomic interventions as novel potential treatment for Alzheimer\u2019s Disease and Parkinson\u2019s Disease. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19103199"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"62","DOI":"10.4331\/wjbc.v11.i2.62","article-title":"Epigenetic basis of Alzheimer disease","volume":"11","year":"2020","journal-title":"World J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"845","DOI":"10.3233\/JAD-132285","article-title":"Age-dependent increment of hydroxymethylation in the brain cortex in the triple-trangenic mouse model of Alzheimer\u2019s disease","volume":"41","author":"Arias","year":"2014","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1016\/j.neurobiolaging.2013.02.021","article-title":"Consistent decrease in global DNA methylation and hydroxymethylation in the hippocampus of Alzheimer\u2019s disease patients","volume":"34","author":"Chouliaras","year":"2013","journal-title":"Neurobiol. Aging"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1016\/j.neurobiolaging.2014.02.002","article-title":"Cross-region reduction in 5-hydroxymethylcytosine in Alzheimer\u2019s disease brain","volume":"31","author":"Conliffe","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1016\/j.neurobiolaging.2008.12.005","article-title":"Epigenetic changes in Alzheimer\u2019s disease: Decrements in DNA methylation","volume":"31","author":"Mastroeni","year":"2010","journal-title":"Neurobiol. Aging"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Mastroeni, D., McKee, A., Grover, A., Rogers, J., and Coleman, P.D. (2009). Epigenetic differences in cortical neurons from a pair of monozygotic twins discordant for Alzheimer\u2019s disease. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0006617"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"E11148","DOI":"10.1073\/pnas.1805436115","article-title":"Inhibition of HDAC3 reverses Alzheimer\u2019s disease-realted pathologies in vitro and in the 3xTg-AD mouse model","volume":"115","author":"Janczura","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1523\/JNEUROSCI.5052-10.2011","article-title":"HDAC3 is a critical negative regulator of long-term memory formation","volume":"31","author":"McQuown","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1111\/acel.12642","article-title":"HDAC3 negatively regulates spatial memory in a mouse model of Alzheimer\u2019s disease","volume":"16","author":"Zhu","year":"2017","journal-title":"Aging Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/ncomms1255","article-title":"The acetylation of tau inhibits its function and promotes pathological tau aggregation","volume":"2","author":"Cohen","year":"2011","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1097\/NEN.0b013e3181922348","article-title":"Sirtuin 1 reduction parallels the accumulation of tau in Alzheimer\u00f1s disease","volume":"68","author":"Julien","year":"2009","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.2174\/1567205013666160401115127","article-title":"Alzheimer\u2019s Disease Genetic Risk Factor APOE-\u03b54 Also Affects Normal Brain Function","volume":"13","author":"Heinsinger","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1136\/jnnp.2004.048983","article-title":"Is there a relation between APOE expression and brain amyloid load in Alzheimer\u2019s disease?","volume":"76","author":"Lambert","year":"2005","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1097\/nen.0b013e318040cfa2","article-title":"Nitric oxide synthase 3-mediated neurodegeneration after intracerebral gene delivery","volume":"66","author":"Jhaveri","year":"2007","journal-title":"J. Neuropath. Exp. Neurol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1097\/01.LAB.0000056995.07053.C0","article-title":"Nitric oxide synthase-3 overexpression causes apoptosis and impairs neuronal mitochondrial function: Relevance to alxheimer\u2019s type degeneration","volume":"83","author":"Chiche","year":"2003","journal-title":"Lab. Investig."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/S0531-5131(03)00076-1","article-title":"COX-2 expression in brains of patients with familiar Alzheimer\u2019s disease","volume":"1252","author":"Choi","year":"2003","journal-title":"Int. Congress Ser."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"307","DOI":"10.2174\/1568007054038201","article-title":"The role of COX-1 and COX-2 in Alzheimer\u2019s Disease Patholgy and the therapeutic potentials of non-steroidal anti-inflammatory drugs","volume":"4","author":"Hoozemans","year":"2005","journal-title":"Curr. Drugs Targets-CNS Neurol. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"927","DOI":"10.14336\/AD.2019.0820","article-title":"Sirtuins and their biological relevance in aging and age-related disorders","volume":"11","author":"Zhao","year":"2020","journal-title":"Aging Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"537","DOI":"10.3389\/fphar.2020.00537","article-title":"Histone deacetylases inhibitors in Neurodegenerative Diseases, Neuroprotection and Neuronals Differentiation","volume":"11","author":"Shukla","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_44","unstructured":"Castelo-Branco, P., and Jeronimo, C. (2020). Epigenetic treatment of neurodegenerative disorders. Histone Modifications in Therapy, Elsevier."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/bpa.12687","article-title":"Aberrant accrual of BIN1 near Alzheimer\u2019s disease amyloid deposits in transgenic models","volume":"29","author":"Andrew","year":"2019","journal-title":"Brain Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"9299","DOI":"10.1074\/jbc.M114.595926","article-title":"COPS5 protein overexpression increases amyloid plaque burden, decreases spinophilin-immuroreactive puncta, and exarcebates learning and memory deficits in the mouse brain","volume":"290","author":"Wang","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e907","DOI":"10.1038\/tp.2016.186","article-title":"Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer\u2019s disease","volume":"6","author":"Jiao","year":"2016","journal-title":"Transl. Psych."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"363","DOI":"10.3389\/fncel.2019.00363","article-title":"Brain-Derived neurotrophic factor: A key molecule for memory in the healthy and pathological brain","volume":"13","author":"Miranda","year":"2019","journal-title":"Front. Cell Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"653267","DOI":"10.3389\/fneur.2021.653267","article-title":"Serum BDNF as a potential biomarker of Alzheimer\u2019s Disease: Verification through assessment of serum, cerebrospinal fluid, and medial temporal lobe atrophy","volume":"12","author":"Mori","year":"2021","journal-title":"Front. Neurol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1007\/s11357-011-9375-5","article-title":"Reversible epigenetic histone modifications and Bdnf expression in neurons with aging and from a mouse model of Alzheimer\u2019s disease","volume":"35","author":"Walker","year":"2012","journal-title":"Age"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Martinez-Iglesias, O., Naidoo, V., Cacabelos, N., and Cacabelos, R. (2022). Epigenetic Biomarkers as diagnostic tools for Neurodegenerative Disorders. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010013"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"757","DOI":"10.3233\/JAD-140033","article-title":"PSEN1 and PSEN2 gene expression in Alzheimer\u2019s disease brain a new approach","volume":"42","author":"Delabio","year":"2014","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1007\/s40263-016-0361-4","article-title":"Apoliporotein E as a therapeutic target in Alzheimer\u2019s disease: A review of basic research and clinical evicende","volume":"30","author":"Yamazaki","year":"2017","journal-title":"CNS Drugs"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1126\/science.1217697","article-title":"ApoE-directed therapeutics rapidly clear beta\u00e1myloid and reverse deficits in AD mouse models","volume":"335","author":"Cramer","year":"2012","journal-title":"Science"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13195-016-0173-2","article-title":"Double-blind, placebo-cpmtrolled, proof-of-concept trial of bexarotene Xin moderate Alzheimer\u2019s disease","volume":"8","author":"Cummings","year":"2016","journal-title":"Alzheimer\u2019s Res. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1080\/17460441.2021.1960502","article-title":"What is the gold standard model for Alzheimer\u2019s disease drug discovery and development?","volume":"16","author":"Cacabelos","year":"2021","journal-title":"Exp. Opin. Drug Discov."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.pharmthera.2018.03.004","article-title":"Sirtuin activators and inhibitors:promises, achievements and challenges","volume":"188","author":"Dai","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1159\/000439214","article-title":"Alterations of the neuroinflammatory markers IL-6 and TRAIL in Alzheimer\u2019s Disease","volume":"5","author":"Wu","year":"2015","journal-title":"Dement. Geriatr. Cogn. Disord. Extra"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"10","DOI":"10.5483\/BMBRep.2020.53.1.309","article-title":"Peripheral inflammatory biomarkers in Alzheimer\u2019s disease: A brief review","volume":"53","author":"Park","year":"2020","journal-title":"BMB Rep."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.yexcr.2004.01.002","article-title":"Interleukin-6 induces Alzheimer-type phosporylation of tau protein by deregulating the cdk5\/p35 pathway","volume":"295","author":"Quintanilla","year":"2004","journal-title":"Exp. Cell Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1023\/A:1022337519035","article-title":"The induction of the TNFalpha death domain signaling patwhway in Alzheimer\u2019s disease brain","volume":"28","author":"Zhao","year":"2003","journal-title":"Neurochem. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1768","DOI":"10.2353\/ajpath.2008.080528","article-title":"Chronic neuron-specific tumor necrosis factor alpha expression enhances the local inflammatory environment ultimately leading to neuronal death in 3xTg-AD mice","volume":"173","author":"Janeksins","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"S35","DOI":"10.1016\/S0885-3924(02)00374-3","article-title":"Evaluation of selective COX-2 inhibitors for the treatment of Alzheimer\u2019s disease","volume":"23","author":"Aisen","year":"2002","journal-title":"J. Pain Symptom Manag."},{"key":"ref_64","doi-asserted-by":"crossref","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":"ref_65","doi-asserted-by":"crossref","unstructured":"Kaur, G., Rathod, S.S.S., Ghoneim, M.M., Alshehri, S., Ahmad, J., Mishra, A., and Alhakamay, N.A. (2022). DNA methylation: A promising approach in manegement of Alzheimer\u2019s Disease and other Neurodegenerative Disorder. Biology, 11.","DOI":"10.3390\/biology11010090"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"476","DOI":"10.3389\/fnins.2019.00476","article-title":"Epigenetic modifications in Alzheimer\u2019s neuropathology and therapeutics","volume":"13","author":"Esposito","year":"2019","journal-title":"Front. Neurosc."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.bbi.2014.11.002","article-title":"Global changes in DNA methylation in Alzheimer\u2019s disease peripheral blood mononuclear cells","volume":"45","author":"Francesco","year":"2015","journal-title":"Brain Behav. Immun. Mar."},{"key":"ref_68","first-page":"159","article-title":"AtreMorine treatment regulates DNA methylation in Neurodegenerative Disorders: Epigenetic and pharmacogenetic studies","volume":"17","author":"Naidoo","year":"2020","journal-title":"Curr. Pharm. Pers. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"226","DOI":"10.3389\/fncel.2015.00226","article-title":"Histone acetylation modifiers in the pathogenesis of Alzheimer\u2019s Disease","volume":"9","author":"Lu","year":"2015","journal-title":"Front Cell Neurosci."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"649","DOI":"10.3389\/fnins.2018.00649","article-title":"The contribution and therapeutic potential of epigenetic modifications in Alzheimer\u2019s Disease","volume":"12","author":"Wood","year":"2018","journal-title":"Front Neurosci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.npep.2018.07.001","article-title":"Sirtuin 1 and Alzheimer\u2019s disease: An up-to-date review","volume":"71","author":"Rizzi","year":"2018","journal-title":"Neuropeptides"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Donmez, G. (2012). The effects of SIRT1 on Alzheimer\u2019s Disease models. Int. J. Alzheimer\u2019s Dis., 2012.","DOI":"10.1155\/2012\/509529"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3680","DOI":"10.1523\/JNEUROSCI.2369-17.2018","article-title":"SIRT1 Deacetylates Tau and Reduces Pathogenic Tau Spread in a Mouse Model of Tauopathy","volume":"38","author":"Min","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2999","DOI":"10.2174\/1568026619666191202155738","article-title":"Cacabelos Neuroprotection with natural antioxidants and nutraceuticals in the context of brain cell degeneration: The epigenetic connection","volume":"19","author":"Carrera","year":"2019","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/j.1474-9726.2006.00259.x","article-title":"Design and synthesis of compounds that extend yeast replicative lifespan","volume":"6","author":"Yang","year":"2007","journal-title":"Aging Cell"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1007\/s10517-020-04986-4","article-title":"Sirtuins as possible predictors of aging and Alzheimer\u2019s Disease development: Verification in the hippocampus and saliva","volume":"169","author":"Pukhalskaia","year":"2020","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Kumar, R., Chaterjee, P., Sharma, P.K., Singh, A.K., Gupta, A., Gill, K., Tripathi, M., Dey, A.B., and Dey, S. (2013). Sirtuin1: A primising serum protein marker for early detection of Alzheimers disease. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061560"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Pradhan, R., Singh, A.K., Kumar, P., Bajpai, S., Pathak, M., Chatterjee, P., Dwivedi, S., Dey, A.B., and Dey, S. (2022). Blood circulatory level of seven sirtuins in Alzheimer\u2019s Disease: Potent biomarker based on translational reseach. Mol. Neurobiol.","DOI":"10.21203\/rs.3.rs-626011\/v1"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Cacabelos, R., Carril, J.C., Cacabelos, N., Zazantsev, A., Vostrov, A.V., Corzo, L., Cacabelos, P., and Goldgaber, D. (2019). Sirtuins in Alzheimer\u2019s Disease-SIRT2-related GenoPhenotypes and implication in Pharmacoepigenetics. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051249"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Xu, K., Dai, X.L., Huang, H.C., and Jiang, Z.F. (2011). Targeting HDACs: A promising therapy for Alzheimer\u2019s Disease. Oxidative Med. Cell. Longev., 2011.","DOI":"10.1155\/2011\/143269"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1080\/10408363.2019.1639129","article-title":"The current status of blood epigenetic biomarkers for dementia","volume":"56","author":"Fransquet","year":"2019","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"487","DOI":"10.3233\/JAD-190023","article-title":"Oral Immunization with Soybean Storage Protein Containing Amyloid-\u03b2 4\u201310 Prevents Spatial Learning Decline","volume":"70","author":"Kawarabayasji","year":"2019","journal-title":"J Alzheimer\u2019s Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.1158\/0008-5472.CAN-15-0205","article-title":"Tristetraprolin Limits Inflammatory Cytokine Production in Tumor-Associated Macrophages in an mRNA Decay-Independent Manner","volume":"75","author":"Kratochvill","year":"2015","journal-title":"Cancer Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.neurobiolaging.2018.10.026","article-title":"Age-dependent behavioral and biochemical characterization of single APP knock-in mouse (APPNL-G-F\/NL-G-F) model of Alzheimer\u2019s disease","volume":"75","author":"Mehla","year":"2019","journal-title":"Neurobiol. Aging"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/5\/2446\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:26:09Z","timestamp":1760135169000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/5\/2446"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,23]]},"references-count":84,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["ijms23052446"],"URL":"https:\/\/doi.org\/10.3390\/ijms23052446","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,23]]}}}