{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T19:51:38Z","timestamp":1792439498076,"version":"4.5.0"},"reference-count":136,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,29]],"date-time":"2023-01-29T00:00:00Z","timestamp":1674950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","award":["2016\/25562-0"],"award-info":[{"award-number":["2016\/25562-0"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","award":["406966\/2016-8"],"award-info":[{"award-number":["406966\/2016-8"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["2016\/25562-0"],"award-info":[{"award-number":["2016\/25562-0"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["406966\/2016-8"],"award-info":[{"award-number":["406966\/2016-8"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["2016\/25562-0"],"award-info":[{"award-number":["2016\/25562-0"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","award":["406966\/2016-8"],"award-info":[{"award-number":["406966\/2016-8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Since Late-onset Alzheimer\u2019s disease (LOAD) derives from a combination of genetic variants and environmental factors, epigenetic modifications have been predicted to play a role in the etiopathology of LOAD. Along with DNA methylation, histone modifications have been proposed as the main epigenetic modifications that contribute to the pathologic mechanisms of LOAD; however, little is known about how these mechanisms contribute to the disease\u2019s onset or progression. In this review, we highlighted the main histone modifications and their functional role, including histone acetylation, histone methylation, and histone phosphorylation, as well as changes in such histone modifications that occur in the aging process and mainly in Alzheimer\u2019s disease (AD). Furthermore, we pointed out the main epigenetic drugs tested for AD treatment, such as those based on histone deacetylase (HDAC) inhibitors. Finally, we remarked on the perspectives around the use of such epigenetics drugs for treating AD.<\/jats:p>","DOI":"10.3390\/genes14020347","type":"journal-article","created":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T06:06:13Z","timestamp":1675058773000},"page":"347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["Histone Modifications in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7084-0337","authenticated-orcid":false,"given":"Dalileia Aparecida","family":"Santana","sequence":"first","affiliation":[{"name":"Department of Morphology & Genetics, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04023-062, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1441-1033","authenticated-orcid":false,"given":"Marilia de Arruda Cardoso","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Morphology & Genetics, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04023-062, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3573-0164","authenticated-orcid":false,"given":"Elizabeth Suchi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Morphology & Genetics, Universidade Federal de S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04023-062, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41593-020-00749-6","article-title":"Natural killers of cognition","volume":"24","author":"Papismadov","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"a028035","DOI":"10.1101\/cshperspect.a028035","article-title":"Pathology of neurodegenerative diseases","volume":"9","author":"Dugger","year":"2017","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/S1474-4422(10)70119-8","article-title":"Alzheimer\u2019s disease: Clinical trials and drug development","volume":"9","author":"Mangialasche","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"139","DOI":"10.2174\/157015906776359577","article-title":"Neuronal Cell Death in Alzheimers Disease and a Neuroprotective Factor, Humanin","volume":"4","author":"Niikura","year":"2006","journal-title":"Curr. Neuropharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.3233\/JAD-140843","article-title":"Biomarkers for preclinical alzheimer\u2019s disease","volume":"42","author":"Tan","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"15056","DOI":"10.1038\/nrdp.2015.56","article-title":"Alzheimer\u2019s disease","volume":"1","author":"Masters","year":"2015","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1016\/j.neuron.2019.01.056","article-title":"A Quarter Century of APOE and Alzheimer\u2019s Disease: Progress to Date and the Path Forward","volume":"101","author":"Belloy","year":"2019","journal-title":"Neuron"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1038\/ng.440","article-title":"Genome-Wide Association Study Identifies Variants at CLU and PICALM Associated with Alzheimer\u2019s Disease, and Shows Evidence for Additional Susceptibility Genes","volume":"41","author":"Harold","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/ng.803","article-title":"Common variants at ABCA7, MS4A6A\/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer\u2019s disease","volume":"43","author":"Hollingworth","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1038\/ng.801","article-title":"Common variants at MS4A4\/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer\u2019s disease","volume":"43","author":"Naj","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.biopsych.2014.05.006","article-title":"Alzheimer\u2019s disease risk genes and mechanisms of disease pathogenesis","volume":"77","author":"Karch","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/s41588-022-01024-z","article-title":"New insights into the genetic etiology of Alzheimer\u2019s disease and related dementias","volume":"54","author":"Bellenguez","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1038\/s41588-021-00921-z","article-title":"A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer\u2019s disease","volume":"53","author":"Wightman","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"20511","DOI":"10.1038\/s41598-021-99352-3","article-title":"Deep post-GWAS analysis identifies potential risk genes and risk variants for Alzheimer\u2019s disease, providing new insights into its disease mechanisms","volume":"11","author":"Wang","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1610","DOI":"10.1038\/s41467-021-21823-y","article-title":"Integration of Alzheimer\u2019s disease genetics and myeloid genomics identifies disease risk regulatory elements and genes","volume":"12","author":"Novikova","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/s41398-018-0150-6","article-title":"GWAS on family history of Alzheimer\u2019s disease","volume":"8","author":"Marioni","year":"2018","journal-title":"Transl. Psychiatry"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1038\/s41588-022-01149-1","article-title":"Genetics of the human microglia regulome refines Alzheimer\u2019s disease risk loci","volume":"54","author":"Kosoy","year":"2022","journal-title":"Nat. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1111\/jnc.14148","article-title":"Epigenetics and DNA methylomic profiling in Alzheimer\u2019s disease and other neurodegenerative diseases","volume":"143","author":"Roubroeks","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"913","DOI":"10.3233\/JAD-170702","article-title":"Role of Genetics and Epigenetics in the Pathogenesis of Alzheimer\u2019s Disease and Frontotemporal Dementia","volume":"62","author":"Fenoglio","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nrn.2017.46","article-title":"The emerging field of epigenetics in neurodegeneration and neuroprotection","volume":"18","author":"Hwang","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/s41586-019-1411-0","article-title":"Advances in epigenetics link genetics to the environment and disease","volume":"571","author":"Cavalli","year":"2019","journal-title":"Nature"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e1600584","DOI":"10.1126\/sciadv.1600584","article-title":"Epigenetics and aging","volume":"2","author":"Pal","year":"2016","journal-title":"Sci. Adv."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/s41593-018-0101-9","article-title":"Dysregulation of the epigenetic landscape of normal aging in Alzheimer\u2019s disease","volume":"21","author":"Nativio","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nrn1604","article-title":"Epigenetic mechanisms in memory formation","volume":"6","author":"Levenson","year":"2005","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3497","DOI":"10.1038\/s41467-021-23636-5","article-title":"Site-specific ubiquitylation acts as a regulator of linker histone H1","volume":"12","author":"Geigges","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1111\/febs.13053","article-title":"Sirtuin-dependent epigenetic regulation in the maintenance of genome integrity","volume":"282","author":"Vaquero","year":"2015","journal-title":"FEBS J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/cr.2011.22","article-title":"Regulation of chromatin by histone modifications","volume":"21","author":"Bannister","year":"2011","journal-title":"Cell Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6754","DOI":"10.1002\/jcp.30337","article-title":"HDAC inhibition prevents hypobaric hypoxia-induced spatial memory impairment through P\u03993K\/GSK3\u03b2\/CREB pathway","volume":"236","author":"Kumar","year":"2021","journal-title":"J. Cell Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/bfgp\/ell028","article-title":"Histone acetylation in gene regulation","volume":"5","author":"Verdone","year":"2006","journal-title":"Brief. Funct. Genom. Proteom."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/nature05772","article-title":"Recovery of learning and memory is associated with chromatin remodelling","volume":"447","author":"Fischer","year":"2007","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/npp.2012.86","article-title":"The role of histone acetylation in memory formation and cognitive impairments","volume":"38","author":"Peixoto","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6690523","DOI":"10.1155\/2021\/6690523","article-title":"The Histone Modifications of Neuronal Plasticity","volume":"2021","author":"Geng","year":"2021","journal-title":"Neural Plast."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"10576","DOI":"10.1523\/JNEUROSCI.1786-08.2008","article-title":"Epigenetic regulation of bdnf gene transcription in the consolidation of fear memory","volume":"28","author":"Lubin","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7603","DOI":"10.1523\/JNEUROSCI.4181-12.2013","article-title":"Nuclear factor \u03baB-dependent histone acetylation is specifically involved in persistent forms of memory","volume":"33","author":"Federman","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_35","first-page":"50","article-title":"NF-\u03baB transcription factor role in consolidation and reconsolidation of persistent memories","volume":"8","author":"Federman","year":"2015","journal-title":"Front. Mol. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.neuron.2004.06.002","article-title":"CBP histone acetyltransferase activity is a critical component of memory consolidation","volume":"42","author":"Korzus","year":"2004","journal-title":"Neuron"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.neuron.2004.05.021","article-title":"Chromatin acetylation, memory, and LTP are impaired in CBP+\/\u2212 mice: A model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration","volume":"42","author":"Malleret","year":"2004","journal-title":"Neuron"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1101\/lm.86605","article-title":"Transgenic mice expressing a truncated form of CREB-binding protein (CBP) exhibit deficits in hippocampal synaptic plasticity and memory storage","volume":"12","author":"Wood","year":"2005","journal-title":"Learn. Mem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"537","DOI":"10.3389\/fphar.2020.00537","article-title":"Histone Deacetylases Inhibitors in Neurodegenerative Diseases, Neuroprotection and Neuronal Differentiation","volume":"11","author":"Shukla","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"108638","DOI":"10.1016\/j.celrep.2020.108638","article-title":"HDAC inhibition results in widespread alteration of the histone acetylation landscape and BRD4 targeting to gene bodies","volume":"34","author":"Slaughter","year":"2021","journal-title":"Cell Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6128","DOI":"10.1523\/JNEUROSCI.0296-07.2007","article-title":"Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB: CBP-dependent transcriptional activation","volume":"27","author":"Vecsey","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1093\/gerona\/gls110","article-title":"Mechanisms of age-related cognitive change and targets for intervention: Epigenetics","volume":"67","author":"Kosik","year":"2012","journal-title":"J. Gerontol. Ser. A Biol. Sci. Med. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"40545","DOI":"10.1074\/jbc.M402229200","article-title":"Regulation of histone acetylation during memory formation in the hippocampus","volume":"279","author":"Levenson","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nrn3427","article-title":"Histone acetylation: Molecular mnemonics on the chromatin","volume":"14","author":"Tsai","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5541","DOI":"10.1038\/sj.onc.1210620","article-title":"Histone deacetylase inhibitors: Molecular mechanisms of action","volume":"26","author":"Xu","year":"2007","journal-title":"Oncogene"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3572","DOI":"10.1172\/JCI79942","article-title":"HDAC inhibitor-dependent transcriptome and memory reinstatement in cognitive decline models","volume":"125","author":"Benito","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1021\/acs.chemrev.6b00801","article-title":"Inhibitors of Protein Methyltransferases and Demethylases","volume":"118","author":"Kaniskan","year":"2018","journal-title":"Chem. Rev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13148-016-0223-4","article-title":"Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy","volume":"8","author":"Morera","year":"2016","journal-title":"Clin. Epigenetics"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1038\/nsmb1338","article-title":"How chromatin-binding modules interpret histone modifications: Lessons from professional pocket pickers","volume":"14","author":"Taverna","year":"2007","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nn1659","article-title":"Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action","volume":"9","author":"Tsankova","year":"2006","journal-title":"Nat. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3589","DOI":"10.1523\/JNEUROSCI.3732-09.2010","article-title":"Histone methylation regulates memory formation","volume":"30","author":"Gupta","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e324","DOI":"10.1038\/emm.2017.11","article-title":"Writing, erasing and reading histone lysine methylations","volume":"49","author":"Hyun","year":"2017","journal-title":"Exp. Mol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e766","DOI":"10.1038\/tp.2016.31","article-title":"Deletion of JMJD2B in neurons leads to defective spine maturation, hyperactive behavior and memory deficits in mouse","volume":"6","author":"Fujiwara","year":"2016","journal-title":"Transl. Psychiatry"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5440","DOI":"10.1523\/JNEUROSCI.0147-12.2012","article-title":"G9a\/GLP histone lysine dimethyltransferase complex activity in the hippocampus and the entorhinal cortex is required for gene activation and silencing during memory consolidation","volume":"32","author":"Gupta","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.4161\/epi.21975","article-title":"Histone phosphorylation: A chromatin modification involved in diverse nuclear events","volume":"7","author":"Rossetto","year":"2012","journal-title":"Epigenetics"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1101\/lm.152906","article-title":"ERK\/MAPK regulates hippocampal histone phosphorylation following contextual fear conditioning","volume":"13","author":"Chwang","year":"2006","journal-title":"Learn. Mem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"4905","DOI":"10.1242\/jcs.00804","article-title":"Chromatin remodeling and neuronal response: Multiple signaling pathways induce specific histone H3 modifications and early gene expression in hippocampal neurons","volume":"116","author":"Crosio","year":"2003","journal-title":"J. Cell Sci."},{"key":"ref_58","first-page":"1","article-title":"Synapse development organized by neuronal activity-regulated immediate-early genes","volume":"50","author":"Kim","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"23304","DOI":"10.1073\/pnas.1913658116","article-title":"Subregion-specific rules govern the distribution of neuronal immediate-early gene induction","volume":"117","author":"Gonzales","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/cdd.2016.161","article-title":"Epigenetic regulation of HDAC1 SUMOylation as an endogenous neuroprotection against A\u03b2 toxicity in a mouse model of Alzheimer\u2019s disease","volume":"24","author":"Tao","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5739","DOI":"10.1021\/acsomega.0c06168","article-title":"Computational Analysis Indicates That PARP1 Acts as a Histone Deacetylases Interactor Sharing Common Lysine Residues for Acetylation, Ubiquitination, and SUMOylation in Alzheimer\u2019s and Parkinson\u2019s Disease","volume":"6","author":"Gupta","year":"2021","journal-title":"ACS Omega"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1111\/acel.12601","article-title":"Molecular and physiological manifestations and measurement of aging in humans","volume":"16","author":"Khan","year":"2017","journal-title":"Aging Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"Blasco","year":"2013","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1089\/ars.2010.3250","article-title":"Epigenetic control of aging","volume":"14","author":"Sedivy","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"10604","DOI":"10.1073\/pnas.0500398102","article-title":"Epigenetic differences arise during the lifetime of monozygotic twins","volume":"102","author":"Fraga","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Larson, K., Yan, S.-J., Tsurumi, A., Liu, J., Zhou, J., Gaur, K., Guo, D., Eickbush, T.H., and Li, W.X. (2012). Heterochromatin formation promotes longevity and represses ribosomal RNA synthesis. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1002473"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Yi, S.J., and Kim, K. (2020). New insights into the role of histone changes in aging. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218241"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"138","DOI":"10.3389\/fgene.2017.00138","article-title":"Epigenetic regulation of cellular senescence and aging","volume":"8","author":"Sidler","year":"2017","journal-title":"Front. Genet."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1146\/annurev-physiol-030212-183715","article-title":"Genome instability and aging","volume":"75","author":"Vijg","year":"2013","journal-title":"Annu. Rev. Physiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1038\/s12276-020-00497-4","article-title":"Heterochromatin: An epigenetic point of view in aging","volume":"52","author":"Lee","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/nrm2238","article-title":"The role of nuclear architecture in genomic instability and ageing","volume":"8","author":"Oberdoerffer","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3389\/fgene.2019.00107","article-title":"Dynamic DNA methylation during aging: A \u201cprophet\u201d of age-related outcomes","volume":"10","author":"Xiao","year":"2019","journal-title":"Front. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.mad.2017.12.002","article-title":"DNA methylation dynamics in aging: How far are we from understanding the mechanisms?","volume":"174","author":"Ciccarone","year":"2018","journal-title":"Mech. Ageing Dev."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.cell.2016.07.050","article-title":"Epigenetic Mechanisms of Longevity and Aging","volume":"166","author":"Sen","year":"2016","journal-title":"Cell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1080\/10409238.2019.1570075","article-title":"Epigenetic changes during aging and their reprogramming potential","volume":"54","author":"Kane","year":"2019","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1126\/science.1186088","article-title":"Altered histone acetylation is associated with age-dependent memory impairment in mice","volume":"328","author":"Peleg","year":"2010","journal-title":"Science"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"8703","DOI":"10.1073\/pnas.0602569103","article-title":"Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature aging","volume":"103","author":"Shumaker","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e64","DOI":"10.1038\/tp.2011.61","article-title":"Disease- and age-related changes in histone acetylation at gene promoters in psychiatric disorders","volume":"1","author":"Tang","year":"2011","journal-title":"Transl. Psychiatry"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.neuron.2015.06.014","article-title":"Critical Role of Histone Turnover in Neuronal Transcription and Plasticity","volume":"87","author":"Maze","year":"2015","journal-title":"Neuron"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1038\/nature08085","article-title":"Histone H4 lysine 16 acetylation regulates cellular lifespan","volume":"459","author":"Dang","year":"2009","journal-title":"Nature"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3125","DOI":"10.1091\/mbc.10.10.3125","article-title":"Modulation of life-span by histone deacetylase genes in Saccharomyces cerevisiae","volume":"10","author":"Kim","year":"1999","journal-title":"Mol. Biol. Cell."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"30483","DOI":"10.3390\/ijms161226236","article-title":"Epigenetics of aging and alzheimer\u2019s disease: Implications for pharmacogenomics and drug response","volume":"16","author":"Cacabelos","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/j.1749-6632.2009.05374.x","article-title":"Biological significance of protein modifications in aging and calorie restriction","volume":"1197","author":"Nakamura","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.phrs.2012.10.010","article-title":"Negative regulation of inflammation by SIRT1","volume":"67","author":"Xie","year":"2013","journal-title":"Pharmacol. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.cell.2008.10.052","article-title":"SIRT6 Links Histone H3 Lysine 9 Deacetylation to NF-\u03baB-Dependent Gene Expression and Organismal Life Span","volume":"136","author":"Kawahara","year":"2009","journal-title":"Cell"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3611","DOI":"10.1523\/JNEUROSCI.2693-15.2016","article-title":"H3K9me3 inhibition improves memory, promotes spine formation, and increases BDNF levels in the aged hippocampus","volume":"36","author":"Snigdha","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_87","first-page":"68","article-title":"Onset of Preclinical Alzheimer Disease in Monozygotic Twins","volume":"2","author":"Konijnenberg","year":"2021","journal-title":"Ann. Neurol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/S1474-4422(20)30412-9","article-title":"APOE and Alzheimer\u2019s disease: Advances in genetics, pathophysiology, and therapeutic approaches","volume":"20","author":"Das","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"740","DOI":"10.2174\/1570159X18666200128125641","article-title":"Alzheimer\u2019s Disorder: Epigenetic Connection and Associated Risk Factors","volume":"18","author":"Sharma","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"579","DOI":"10.3389\/fgene.2018.00579","article-title":"The Epigenetics of Alzheimer\u2019s Disease: Factors and Therapeutic Implications","volume":"9","author":"Liu","year":"2018","journal-title":"Front. Genet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.trsl.2014.05.006","article-title":"Epigenomics of Alzheimer\u2019s disease","volume":"165","author":"Bennett","year":"2014","journal-title":"Transl. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1038\/nn.3786","article-title":"Alzheimer\u2019s disease: Early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci","volume":"17","author":"Srivastava","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2246","DOI":"10.1038\/s41467-019-10101-7","article-title":"Epigenetic dysregulation of enhancers in neurons is associated with Alzheimer\u2019s disease pathology and cognitive symptoms","volume":"10","author":"Li","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1002\/pmic.201200010","article-title":"Targeted proteomics for quantification of histone acetylation in Alzheimer\u2019s disease","volume":"12","author":"Zhang","year":"2012","journal-title":"Proteomics"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/nature13163","article-title":"REST and stress resistance in ageing and Alzheimer\u2019s disease","volume":"507","author":"Lu","year":"2014","journal-title":"Nature"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41593-018-0291-1","article-title":"Epigenome-wide study uncovers large-scale changes in histone acetylation driven by tau pathology in aging and Alzheimer\u2019s human brains","volume":"22","author":"Klein","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1618","DOI":"10.1038\/s41593-018-0253-7","article-title":"A histone acetylome-wide association study of Alzheimer\u2019s disease identifies disease-associated H3K27ac differences in the entorhinal cortex","volume":"21","author":"Marzi","year":"2018","journal-title":"Nat. Neurosci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1038\/s41588-020-0696-0","article-title":"An integrated multi-omics approach identifies epigenetic alterations associated with Alzheimer\u2019s disease","volume":"52","author":"Nativio","year":"2020","journal-title":"Nat. Genet."},{"key":"ref_99","unstructured":"GBD 2015 Neurological Disorders Collaborator Group (2017). Global, regional, and national burden of neurological disorders during 1990\u20132015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet Neurol., 16, 877\u2013897."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.tcb.2011.11.001","article-title":"Histone methylation makes its mark on longevity","volume":"22","author":"Han","year":"2012","journal-title":"Trends Cell Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1093\/brain\/awy354","article-title":"Inhibition of EHMT1\/2 rescues synaptic and cognitive functions for Alzheimer\u2019s disease","volume":"142","author":"Zheng","year":"2019","journal-title":"Brain"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1038\/nature14252","article-title":"Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer\u2019s disease","volume":"518","author":"Gjoneska","year":"2015","journal-title":"Nature"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"eabc8096","DOI":"10.1126\/sciadv.abc8096","article-title":"Tar geting histone K4 trimethylation for treatment of cognitive and synaptic deficits in mouse models of Alzheimer\u2019s disease","volume":"6","author":"Cao","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"8481","DOI":"10.18632\/oncotarget.7380","article-title":"Potential role of PCTAIRE-2, PCTAIRE-3 and P-Histone H4 in amyloid precursor protein-dependent Alzheimer pathology","volume":"7","author":"Chaput","year":"2016","journal-title":"Oncotarget"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s11357-008-9050-7","article-title":"Evidence of DNA damage in Alzheimer disease: Phosphorylation of histone H2AX in astrocytes","volume":"30","author":"Myung","year":"2008","journal-title":"Age"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1007\/s00401-003-0684-3","article-title":"Ectopic localization of phosphorylated histone H3 in Alzheimer\u2019s disease: A mitotic catastrophe?","volume":"105","author":"Ogawa","year":"2003","journal-title":"Acta Neuropathol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e132","DOI":"10.1038\/tp.2012.55","article-title":"Epigenetic modifications in frontal cortex from Alzheimer\u2019s disease and bipolar disorder patients","volume":"2","author":"Rao","year":"2012","journal-title":"Transl. Psychiatry"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12014-015-9098-1","article-title":"Histone post-translational modifications in frontal cortex from human donors with Alzheimer\u2019s disease","volume":"12","author":"Anderson","year":"2015","journal-title":"Clin. Proteom."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"25628","DOI":"10.1038\/srep25628","article-title":"P53-dependent SIRT6 expression protects A\u03b242-induced DNA damage","volume":"6","author":"Jung","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S1474-4422(11)70013-8","article-title":"The sirtuin pathway in ageing and Alzheimer disease: Mechanistic and therapeutic considerations","volume":"10","author":"Bonda","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"E11148","DOI":"10.1073\/pnas.1805436115","article-title":"Inhibition of HDAC3 reverses Alzheimer\u2019s disease-related 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_112","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3389\/fnagi.2019.00149","article-title":"Taking advantage of the selectivity of histone deacetylases and phosphodiesterase inhibitors to design better therapeutic strategies to treat Alzheimer\u2019s disease","volume":"11","author":"Muruzabal","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Bagheri, A., Habibzadeh, P., Razavipour, S.F., Volmar, C.-H., Chee, N.T., Brothers, S.P., Wahlestedt, C., Mowla, S.J., and Faghihi, M.A. (2019). HDAC inhibitors induce BDNF expression and promote neurite outgrowth in human neural progenitor cells-derived neurons. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20051109"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1038\/nrd2681","article-title":"Therapeutic application of histone deacetylase inhibitors for central nervous system disorders","volume":"7","author":"Kazantsev","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"2781","DOI":"10.1084\/jem.20081588","article-title":"Valproic acid inhibits a\u03b2 production, neuritic plaque formation, and behavioral deficits in alzheimer\u2019s disease mouse models","volume":"205","author":"Qing","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3389\/fnagi.2019.00062","article-title":"Valproic Acid Stimulates Hippocampal Neurogenesis via Activating the Wnt\/\u03b2-Catenin Signaling Pathway in the APP\/PS1\/Nestin-GFP Triple Transgenic Mouse Model of Alzheimer\u2019s Disease","volume":"11","author":"Zeng","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1038\/npp.2008.229","article-title":"Phenylbutyrate ameliorates cognitive deficit and reduces tau pathology in an alzheimer\u2019s disease mouse model","volume":"34","author":"Ricobaraza","year":"2009","journal-title":"Neuropsychopharmacology"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1002\/hipo.20883","article-title":"Phenylbutyrate rescues dendritic spine loss associated with memory deficits in a mouse model of Alzheimer disease","volume":"22","author":"Ricobaraza","year":"2012","journal-title":"Hippocampus"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/npp.2009.197","article-title":"Inhibitors of class 1 histone deacetylases reverse contextual memory deficits in a mouse model of alzheimer\u2019s disease","volume":"35","author":"Kilgore","year":"2009","journal-title":"Neuropsychopharmacology"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1007\/s11064-021-03367-1","article-title":"Treatment with Histone Deacetylase Inhibitor Attenuates Peripheral Inflammation-Induced Cognitive Dysfunction and Microglial Activation: The Effect of SAHA as a Peripheral HDAC Inhibitor","volume":"46","author":"Takada","year":"2021","journal-title":"Neurochem. Res."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Hanson, J.E., La, H., Plise, E., Chen, Y.-H., Ding, X., Hanania, T., Sabath, E.V., Alexandrov, V., Brunner, D., and Leahy, E. (2013). SAHA Enhances Synaptic Function and Plasticity In Vitro but Has Limited Brain Availability In Vivo and Does Not Impact Cognition. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0069964"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s12017-021-08660-4","article-title":"Repurposing Vorinostat for the Treatment of Disorders Affecting Brain","volume":"23","author":"Athira","year":"2021","journal-title":"Neuromol. Med."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1021\/acschemneuro.1c00022","article-title":"Neuroprotective Efficacy of Co-Encapsulated Rosiglitazone and Vorinostat Nanoparticle on Streptozotocin Induced Mice Model of Alzheimer Disease","volume":"12","author":"Sarathlal","year":"2021","journal-title":"ACS Chem. Neurosci."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13195-020-00746-8","article-title":"Trichostatin A ameliorates Alzheimer\u2019s disease-related pathology and cognitive deficits by increasing albumin expression and A\u03b2 clearance in APP\/PS1 mice","volume":"13","author":"Su","year":"2021","journal-title":"Alzheimers Res. Ther."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"113874","DOI":"10.1016\/j.ejmech.2021.113874","article-title":"Inhibition of Histone Deacetylase 6 (HDAC6) as a therapeutic strategy for Alzheimer\u2019s disease: A review (2010\u20132020)","volume":"226","author":"Li","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"4577","DOI":"10.1111\/bcp.14889","article-title":"Recent developments of HDAC inhibitors: Emerging indications and novel molecules","volume":"87","author":"Bondarev","year":"2021","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Wang, Z., Yang, D., Zhang, X., Li, T., Li, J., Tang, Y., and Le, W. (2011). Hypoxia-Induced Down-Regulation of Neprilysin by Histone Modification in Mouse Primary Cortical and Hippocampal Neurons. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019229"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Nikolac Perkovic, M., Videtic Paska, A., Konjevod, M., Kouter, K., Svob Strac, D., Nedic Erjavec, G., and Pivac, N. (2021). Epigenetics of Alzheimer\u2019s Disease. Biomolecules, 11.","DOI":"10.3390\/biom11020195"},{"key":"ref_129","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_130","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.celrep.2017.06.072","article-title":"KMT2A and KMT2B Mediate Memory Function by Affecting Distinct Genomic Regions","volume":"20","author":"Kerimoglu","year":"2017","journal-title":"Cell Rep."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/s41467-017-00922-9","article-title":"LSD1 protects against hippocampal and cortical neurodegeneration","volume":"8","author":"Christopher","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/ncomms1997","article-title":"Dynamic histone marks in the hippocampus and cortex facilitate memory consolidation","volume":"3","author":"Woldemichael","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"12732","DOI":"10.1523\/JNEUROSCI.2522-07.2007","article-title":"The nuclear kinase mitogen- and stress-activated protein kinase 1 regulates hippocampal chromatin remodeling in memory formation","volume":"27","author":"Chwang","year":"2007","journal-title":"J. Neurosci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1101\/gad.373706","article-title":"DNA damage triggers nucleotide excision repair-dependent monoubiquitylation of histone H2A","volume":"20","author":"Bergink","year":"2006","journal-title":"Genes Dev."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"4","DOI":"10.3389\/fnmol.2016.00004","article-title":"The ubiquitin-proteasome system: Potential therapeutic targets for alzheimer\u2019s disease and spinal cord injury","volume":"9","author":"Gong","year":"2016","journal-title":"Front. Mol. Neurosci."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"23658","DOI":"10.1074\/jbc.M203690200","article-title":"SUMO-1 modification of histone deacetylase 1 (HDAC1) modulates its biological activities","volume":"277","author":"David","year":"2002","journal-title":"J. Biol. Chem."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/2\/347\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:19:05Z","timestamp":1760120345000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/2\/347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,29]]},"references-count":136,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["genes14020347"],"URL":"https:\/\/doi.org\/10.3390\/genes14020347","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,29]]}}}