title: New assays and approaches for discovery and design of Sirtuin modulators.
abstract: BACKGROUND
  Sirtuins are an evolutionarily conserved family of NAD(+)-dependent protein lysine deacylases. In mammals, 7 Sirtuin isoforms control various functions in metabolism, stress responses and aging processes. Sirtuins are considered attractive therapeutic targets for metabolic and aging-related diseases, such as metabolic syndrome and neurodegenerative disorders. Extensive development efforts on small-molecule Sirtuin inhibitors and activators have yielded few potent and selective compounds, partly due to shortcomings of available assays and a lack of mechanistic characterization of identified compounds.
  
  
  METHODS
  The authors describe the developments in analyzing Sirtuin activity and conceptual advances in the identification, improvement and design of Sirtuin-modulating compounds. They also review the application of these methods and concepts for the development and mechanistic characterization of Sirtuin modulators.
  
  
  CONCLUSIONS
  Novel assays and experimental approaches for studying Sirtuin activity have been instrumental for major progress in understanding functions of Sirtuins and how these enzymes can be modulated with drugs. The improved tools and mechanistic insights now enable a more efficient development of Sirtuin modulators for in vivo studies and therapeutic applications.
authors.affiliation: Martin Luther University Halle-Wittenberg, Institute for Biochemistry and Biotechnology, Department of Enzymology , 06108 Halle , Germany.
authors.forename: Mike
authors.initials: M
authors.lastname: Schutkowski
authors.forename: Frank
authors.initials: F
authors.lastname: Fischer
authors.forename: Claudia
authors.initials: C
authors.lastname: Roessler
authors.forename: Clemens
authors.initials: C
authors.lastname: Steegborn
mesh_terms: D000818:Animals; D001681:Biological Assay; D055808:Drug Discovery; D006801:Humans; D037761:Sirtuins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D037761:Sirtuins