Sirtuin functions and modulation: from chemistry to the clinic

Clin Epigenetics. 2016 May 25:8:61. doi: 10.1186/s13148-016-0224-3. eCollection 2016.

Abstract

Sirtuins are NAD(+)-dependent histone deacetylases regulating important metabolic pathways in prokaryotes and eukaryotes and are involved in many biological processes such as cell survival, senescence, proliferation, apoptosis, DNA repair, cell metabolism, and caloric restriction. The seven members of this family of enzymes are considered potential targets for the treatment of human pathologies including neurodegenerative diseases, cardiovascular diseases, and cancer. Furthermore, recent interest focusing on sirtuin modulators as epigenetic players in the regulation of fundamental biological pathways has prompted increased efforts to discover new small molecules able to modify sirtuin activity. Here, we review the role, mechanism of action, and biological function of the seven sirtuins, as well as their inhibitors and activators.

Keywords: Cancer; Drug discovery; Epigenetics; Neurodegeneration; SIRT modulators; Sirtuins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Proliferation
  • Cell Survival
  • Cellular Senescence
  • DNA Repair
  • Enzyme Inhibitors / pharmacology*
  • Epigenesis, Genetic
  • Gene Expression Regulation / drug effects
  • Humans
  • Sirtuins / antagonists & inhibitors
  • Sirtuins / metabolism*

Substances

  • Enzyme Inhibitors
  • Sirtuins