{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T18:19:52Z","timestamp":1791656392881,"version":"4.3.4"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0 http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>\n                    Sirtuin 2, a NAD\n                    <jats:sup>+<\/jats:sup>\n                    -dependent deacetylase of the sirtuin family, has emerged as a pivotal regulator of brain physiology and pathology. Highly expressed in the central nervous system, sirtuin 2 exerts diverse and cell-type-specific functions in neurons, oligodendrocytes, astrocytes, and microglia. This review provides a comprehensive synthesis of current knowledge on sirtuin 2 within the central nervous system, emphasizing its multifaceted roles across different brain cell types and its potential as a therapeutic target in neurological disorders. In neurons, sirtuin 2 modulates axonal dynamics, mitochondrial function, and synaptic plasticity, displaying both neuroprotective and detrimental effects depending on context. In oligodendrocytes, sirtuin 2 is essential for differentiation, myelination, and axonal metabolic support via exosomal transfer, while its dysregulation contributes to hypomyelination and age-related myelin decline. In astrocytes, sirtuin 2 influences metabolism, senescence, and reactive gliosis, exerting protective effects under physiological conditions but potentially aggravating pathology after injury or in Alzheimer\u2019s disease. In microglia, sirtuin 2 modulates inflammatory responses, acting as either a suppressor or amplifier of neuroinflammation depending on the stimulus and disease context. The dual, sometimes opposing, functions of sirtuin 2 across central nervous system cell types underscore the complexity of its regulation and the need for context-dependent therapeutic approaches. By integrating evidence from genetic and pharmacological studies, this review delineates the cell-specific mechanisms through which sirtuin 2 influences central nervous system physiology and pathology. Understanding these heterogeneous and context-dependent actions is essential to harness the therapeutic potential of sirtuin 2 modulation in neurodegenerative, inflammatory, and demyelinating diseases.\n                  <\/jats:p>","DOI":"10.4103\/nrr.nrr-d-25-01461","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T09:00:22Z","timestamp":1779872422000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Role of sirtuin 2 in the brain is cell-type and context-dependent: Implications for therapeutic targeting"],"prefix":"10.4103","author":[{"given":"Maider","family":"Garmendia-Berges","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Division of Pharmacology, University of Navarra, Pamplona, Spain"},{"name":"IdISNA, Navarra Institute for Health Research, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5695-5787","authenticated-orcid":false,"given":"Elena","family":"Puerta","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Division of Pharmacology, University of Navarra, Pamplona, Spain"},{"name":"IdISNA, Navarra Institute for Health Research, Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,5,14]]},"container-title":["Neural Regeneration Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/NRR.NRR-D-25-01461","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T19:28:02Z","timestamp":1786735682000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/NRR.NRR-D-25-01461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,14]]},"references-count":0,"URL":"https:\/\/doi.org\/10.4103\/nrr.nrr-d-25-01461","relation":{},"ISSN":["1673-5374","1876-7958"],"issn-type":[{"value":"1673-5374","type":"print"},{"value":"1876-7958","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,14]]},"assertion":[{"value":"2025-09-30","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-18","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}