{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:58:24Z","timestamp":1792119504621,"version":"4.4.0"},"reference-count":111,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)"},{"name":"Minist\u00e9rio da Sa\u00fade"},{"name":"Departamento de Ci\u00eancia e Tecnologia (MS-DECIT)"},{"name":"Funda\u00e7\u00e3o Carlos Chagas Filho de Amparo \u00e0 Pesquisa do Estado do Rio de Janeiro (FAPERJ)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Histone deacetylases (HDACs) are key epigenetic regulators that influence chromatin remodeling, gene expression, and cellular plasticity in the central nervous system (CNS). This review provides a comprehensive overview of the classification and functional diversity of HDACs, with particular emphasis on their roles in neural progenitor cells, mature neurons, and glial populations. In neural stem and progenitor cells, HDACs modulate neurogenesis, fate specification, and lineage commitment. In differentiated neurons, HDACs govern synaptic plasticity, memory formation, and survival. In glial cells, including astrocytes and microglia, HDACs orchestrate inflammatory responses, redox balance, and metabolic adaptations. We further examine the dysregulation of HDAC expression and activity in major neurodegenerative diseases, including Alzheimer\u2019s disease and Parkinson\u2019s disease. Evidence from human post-mortem brain studies reveals region- and isoform-specific alterations in HDAC expression, which are closely associated with cognitive decline, mitochondrial dysfunction, and neuroinflammation. Preclinical studies support the use of HDAC inhibitors (HDACi) as neuroprotective agents, capable of restoring acetylation homeostasis, reducing neuroinflammation, and improving neuronal function. Given the relevance of HDACi, we summarize current clinical studies assessing the safety of these compounds in the context of tumor biology, as well as their potential future applications in neurodegenerative diseases. Together, this review underscores the dual significance of HDACs as biomarkers and therapeutic targets in the context of CNS disorders.<\/jats:p>","DOI":"10.3390\/cells14171338","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T09:08:52Z","timestamp":1756458532000},"page":"1338","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["HDACs in the Brain: From Chromatin Remodeling to Neurodegenerative Disease"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2986-4043","authenticated-orcid":false,"given":"Luan Pereira","family":"Diniz","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Investiga\u00e7\u00e3o Metab\u00f3lica Associada ao Envelhecimento, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4148-4243","authenticated-orcid":false,"given":"Pedro de Sena Murteira","family":"Pinheiro","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Avalia\u00e7\u00e3o e S\u00edntese de Subst\u00e2ncias Bioativas (LASSBio), Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0121-3011","authenticated-orcid":false,"given":"Lucas S.","family":"Franco","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Avalia\u00e7\u00e3o e S\u00edntese de Subst\u00e2ncias Bioativas (LASSBio), Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2966-0638","authenticated-orcid":false,"given":"Fl\u00e1via Carvalho Alcantara","family":"Gomes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Neurobiologia Celular, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, RJ, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/s41392-025-02145-7","article-title":"Antiageing strategy for neurodegenerative diseases: From mechanisms to clinical advances","volume":"10","author":"Jiang","year":"2025","journal-title":"Signal Transduct. 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