Sirtuins as pharmacological targets in neurodegenerative and neuropsychiatric disorders

Histone deacetylases (HDACs) are enzymes that regulate several processes, such as transcription, cell proliferation, differentiation and development. HDACs are classified as either Zn²⁺ -dependent or NAD⁺ -dependent 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 Zn²⁺ -dependent HDACs in the development of these diseases, although there is growing evidence showing that the NAD⁺ -dependent HDACs, known as sirtuins, are also very promising targets. This possibility has been strengthened by reports of decreased levels of NAD⁺ 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. LINKED ARTICLES: This article is part of a themed issue on Building Bridges in Neuropharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.8/issuetoc.