Pharmacological manipulations of CNS sirtuins: potential effects on metabolic homeostasis.
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.
Department of Internal Medicine (Division of Hypothalamic Research), The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd-Room Y6-220C, Dallas, TX 75390-9077, USA.
Giorgio
G
Ramadori
Roberto
R
Coppari
D000375:Aging / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D037761:Sirtuins / Q000378:metabolism / Q000502:physiology*; D013379:Substrate Specificity
D037761:Sirtuins