title: The Current State of NAD+-Dependent Histone Deacetylases (Sirtuins) as Novel Therapeutic Targets.
abstract: Sirtuins are NAD+-dependent protein deacylases that cleave off acetyl, as well as other acyl groups, from the ε-amino group of lysines in histones and other substrate proteins. Seven sirtuin isotypes (Sirt1-7) have been identified in mammalian cells. As sirtuins are involved in the regulation of various physiological processes such as cell survival, cell cycle progression, apoptosis, DNA repair, cell metabolism, and caloric restriction, a dysregulation of their enzymatic activity has been associated with the pathogenesis of neoplastic, metabolic, infectious, and neurodegenerative diseases. Thus, sirtuins are promising targets for pharmaceutical intervention. Growing interest in a modulation of sirtuin activity has prompted the discovery of several small molecules, able to inhibit or activate certain sirtuin isotypes. Herein, we give an update to our previous review on the topic in this journal (Schemies, 2010), focusing on recent developments in sirtuin biology, sirtuin modulators, and their potential as novel therapeutic agents.
authors.affiliation: Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schiedel
authors.affiliation: Department of Pharmaceutical Chemistry, Martin-Luther Universität Halle-Wittenberg, Halle/Saale, Germany.
authors.forename: Dina
authors.initials: D
authors.lastname: Robaa
authors.affiliation: Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Rumpf
authors.affiliation: Department of Pharmaceutical Chemistry, Martin-Luther Universität Halle-Wittenberg, Halle/Saale, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sippl
authors.affiliation: Institute of Pharmaceutical Sciences, Albert-Ludwigs-Universität Freiburg, Freiburg, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Jung
mesh_terms: D000818:Animals; D056545:Group III Histone Deacetylases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D058990:Molecular Targeted Therapy
chemical_list: D056572:Histone Deacetylase Inhibitors; D056545:Group III Histone Deacetylases
keywords: KDAC; epigenetics; lysine deacetylases; resveratrol; sirtuins