After the Grape Rush: Sirtuins as Epigenetic Drug Targets in Neurodegenerative Disorders

Bioorg Med Chem. 2011 Jun 15;19(12):3616-24. doi: 10.1016/j.bmc.2011.01.018. Epub 2011 Jan 15.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Epigenesis, Genetic*
  • Humans
  • Neurodegenerative Diseases / drug therapy*
  • Parkinson Disease / drug therapy
  • Resveratrol
  • Sirtuins / genetics
  • Sirtuins / metabolism*
  • Stilbenes / pharmacology*
  • Stilbenes / therapeutic use*
  • Up-Regulation / drug effects*

Substances

  • Enzyme Inhibitors
  • Stilbenes
  • Sirtuins
  • Resveratrol