NAD(+) -dependent histone deacetylases (sirtuins) as novel therapeutic targets.
Histone deacetylases (HDACs) are enzymes that cleave off acetyl groups from acetyl-lysine residues in histones and various nonhistone proteins. Four different classes of HDACs have been identified in humans so far. Although classes I, II, and IV are zinc-dependent amidohydrolases, class III HDACs depend on nicotinamide adenine dinucleotide (NAD(+)) for their catalytic activity. According to their homology to Sir2p, a yeast histone deacetylase, the class III is also termed sirtuins. Seven members have been described in humans so far. As sirtuins are involved in many physiological and pathological processes, their activity has been associated with the pathogenesis of cancer, HIV, metabolic, or neurological diseases. Herein, we present an overview over sirtuins including their biology, targets, inhibitors, and activators and their potential as new therapeutic agents.
Schemies
Jörg
J
Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Albertstr. 25, 79104 Freiburg, Germany.
Uciechowska
Urszula
U
Sippl
Wolfgang
W
Jung
Manfred
M
D000818:Animals; D044127:Epigenesis, Genetic; D015658:HIV Infections / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D009243:NAD / Q000737:chemistry*; D009369:Neoplasms / Q000378:metabolism; D009536:Niacinamide / Q000737:chemistry; D011485:Protein Binding; D000077185:Resveratrol; D015398:Signal Transduction; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000378:metabolism; D056565:Sirtuin 2 / Q000737:chemistry / Q000378:metabolism; D037761:Sirtuins / Q000737:chemistry*; D013267:Stilbenes / Q000494:pharmacology
D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D013267:Stilbenes; D009243:NAD; D009536:Niacinamide; C087778:SIR2 protein, S cerevisiae; C474199:SIRT2 protein, human; D056565:Sirtuin 2; D037761:Sirtuins; D000077185:Resveratrol