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Class III histone deacetylases (sirtuins) are becoming increasingly recognized as important epigenetic drug targets in cancer and metabolic disorders. As key regulators involved in numerous cellular signalling pathways, sirtuins are also emerging as potential targets in various neurodegenerative diseases such as Alzheimer, Parkinson's disease and others, thus suggesting modulation of sirtuin activity could provide an interesting and novel therapeutic option. In particular, much attention has been raised by neuroprotective effects attributed to SIRT1 activation due to genetically induced sirtuin overexpression or administration of resveratrol, a natural compound found in the skin of red grapes and also in wine. Similarly, also sirtuin inhibitors display benefits in various neuropathologic disease models. In light of the growing interest in sirtuin modulation and with regard to the lack of conclusive data on small molecule activators of sirtuins this review recapitulates the known facts about sirtuins and their relevance in neurodegenerative diseases.

Original publication

DOI

10.1016/j.bmc.2011.01.018

Type

Journal article

Journal

Bioorg Med Chem

Publication Date

15/06/2011

Volume

19

Pages

3616 - 3624

Keywords

Alzheimer Disease, Enzyme Inhibitors, Epigenesis, Genetic, Humans, Neurodegenerative Diseases, Parkinson Disease, Sirtuins, Stilbenes, Up-Regulation