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HDACs are classified as either Zn<jats:sup>2+<\/jats:sup>\u2010dependent or NAD<jats:sup>+<\/jats:sup>\u2010dependent enzymes. Over the years, experimental and clinical evidence has demonstrated that HDAC modulation is a critical process in neurodegenerative and psychiatric disorders. Nevertheless, most of the studies have focused on the role of Zn<jats:sup>2+<\/jats:sup>\u2010dependent HDACs in the development of these diseases, although there is growing evidence showing that the NAD<jats:sup>+<\/jats:sup>\u2010dependent HDACs, known as sirtuins, are also very promising targets. This possibility has been strengthened by reports of decreased levels of NAD<jats:sup>+<\/jats:sup> in CNS disorders, which can lead to alterations in sirtuin activation and therefore result in increased pathology. In this review, we discuss the role of sirtuins in neurodegenerative and neuropsychiatric disorders as well the possible rationale for them to be considered as pharmacological targets in future therapeutic interventions.<\/jats:p><\/jats:sec><jats:sec><jats:title>LINKED ARTICLES<\/jats:title><jats:p>This article is part of a themed issue on Building Bridges in Neuropharmacology. To view the other articles in this section visit <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v179.8\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v179.8\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15570","type":"journal-article","created":{"date-parts":[[2021,5,24]],"date-time":"2021-05-24T17:06:18Z","timestamp":1621875978000},"page":"1496-1511","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Sirtuins as pharmacological targets in neurodegenerative and neuropsychiatric disorders"],"prefix":"10.1111","volume":"179","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9437-5393","authenticated-orcid":false,"given":"Jefferson A.","family":"Leite","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Immunology, Ribeir\u00e3o Preto School of Medicine University of S\u00e3o Paulo  Ribeir\u00e3o Preto S\u00e3o Paulo Brazil"},{"name":"Department of Immunology, Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6835-3329","authenticated-orcid":false,"given":"Bruno","family":"Ghirotto","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8807-0614","authenticated-orcid":false,"given":"Vitor P.","family":"Targhetta","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7223-914X","authenticated-orcid":false,"given":"Jean","family":"de Lima","sequence":"additional","affiliation":[{"name":"Department of Immunology, Institute of Biomedical Sciences University of S\u00e3o Paulo  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5436-1248","authenticated-orcid":false,"given":"Niels O. 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