Protective effects and mechanisms of sirtuins in the nervous system

Prog Neurobiol. 2011 Nov;95(3):373-95. doi: 10.1016/j.pneurobio.2011.09.001. Epub 2011 Sep 10.


Silent information regulator two proteins (sirtuins or SIRTs) are a group of histone deacetylases whose activities are dependent on and regulated by nicotinamide adenine dinucleotide (NAD(+)). They suppress genome-wide transcription, yet upregulate a select set of proteins related to energy metabolism and pro-survival mechanisms, and therefore play a key role in the longevity effects elicited by calorie restriction. Recently, a neuroprotective effect of sirtuins has been reported for both acute and chronic neurological diseases. The focus of this review is to summarize the latest progress regarding the protective effects of sirtuins, with a focus on SIRT1. We first introduce the distribution of sirtuins in the brain and how their expression and activity are regulated. We then highlight their protective effects against common neurological disorders, such as cerebral ischemia, axonal injury, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Finally, we analyze the mechanisms underlying sirtuin-mediated neuroprotection, centering on their non-histone substrates such as DNA repair enzymes, protein kinases, transcription factors, and coactivators. Collectively, the information compiled here will serve as a comprehensive reference for the actions of sirtuins in the nervous system to date, and will hopefully help to design further experimental research and expand sirtuins as therapeutic targets in the future.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Brain Chemistry / genetics
  • Caloric Restriction
  • Cell Nucleus / drug effects
  • Cytosol / drug effects
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Histone Deacetylases / physiology
  • Humans
  • Longevity / physiology
  • Mitochondria / drug effects
  • Nervous System Physiological Phenomena* / drug effects
  • Neurodegenerative Diseases / drug therapy
  • Neuroprotective Agents*
  • Sirtuin 1 / metabolism
  • Sirtuin 1 / physiology
  • Sirtuins / genetics
  • Sirtuins / metabolism
  • Sirtuins / pharmacology
  • Sirtuins / physiology*
  • Sirtuins / therapeutic use


  • Neuroprotective Agents
  • SIRT1 protein, human
  • Sirtuin 1
  • Sirtuins
  • Histone Deacetylases