Scientific article
Open access

Pharmacological manipulations of CNS sirtuins: potential effects on metabolic homeostasis

Published inPharmacological research, vol. 62, no. 1, p. 48-54
Publication date2010-07
First online date2010-02-06

Sirtuins are deacetylases and/or mono-ADP-ribosyltransferases found in organisms ranging from bacteria to humans. These enzymes use oxidized nicotinamide adenine dinucleotide (NAD(+)) and a long array of different proteins (e.g.: histones, transcription factors, cofactors, members of the electron transport chain, etc.) as substrates. Sirtuins-mediated reactions yield deacetylated proteins, nicotinamide (NAM) and 2'-O-acetyl-ADP-ribose (O-AADPr) or mono-ADP-ribosylated proteins and NAM. As these post-translational modifications change the activity of their targets and sirtuins depend on NAD(+) to function, these enzymes are thought to link metabolic statuses with cellular gene expression, activity and fate; as such sirtuins are thought to be bona fide metabolic-sensor proteins. Due to their diverse targets, sirtuins affect metabolism, senescence, longevity, circadian rhythms and many other biological and physiological programs. In this review we focus on their known roles on metabolic homeostasis with particular emphasis on their functions in neurons within the central nervous system (CNS). We also touch upon the possible metabolic outcomes of pharmacological manipulations of CNS sirtuins.

  • Aging / drug effects
  • Aging / metabolism
  • Animals
  • Brain / drug effects
  • Brain / enzymology
  • Brain / metabolism
  • Cell Nucleus / drug effects
  • Cell Nucleus / enzymology
  • Cell Nucleus / metabolism
  • Energy Metabolism / drug effects
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / enzymology
  • Mitochondria / metabolism
  • Neurons / drug effects
  • Neurons / enzymology
  • Neurons / metabolism
  • Sirtuins / metabolism
  • Sirtuins / physiology
  • Substrate Specificity
Affiliation Not a UNIGE publication
  • NIDDK NIH HHS - [R01 DK080836]
  • NIDDK NIH HHS - [R01 DK080836-01A2]
  • NIDDK NIH HHS - [DK080836]
Citation (ISO format)
RAMADORI, Giorgio, COPPARI, Roberto. Pharmacological manipulations of CNS sirtuins: potential effects on metabolic homeostasis. In: Pharmacological research, 2010, vol. 62, n° 1, p. 48–54. doi: 10.1016/j.phrs.2010.02.002
Main files (1)
Article (Accepted version)
ISSN of the journal1043-6618

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