Human sirtuins: An overview of an emerging drug target in age-related diseases and cancer

Alessandra Donadini, Camillo Rosano, Lamberto Felli, Marco Ponassi

Research output: Contribution to journalArticlepeer-review

Abstract

Sir2-like proteins (Sirtuins) are a class of enzymes conserved throughout the kingdoms of life. In fact, from Archaea to Mammals, these (class III) NAD+-dependent deacetylases catalyse the removal of the acetyl moiety from a substrate protein. Sirtuins show a conserved central catalytic domain with two more variable amino-and carboxy-terminal flanking regions. Amino acid comparison of these central conserved catalytic core sequences allows us to divide Sirtuins into five different classes (I, II, III, IV and U). These proteins differ in their subcellular localization (i.e. in Eukaryotes they can be found in the nucleus, cytoplasm or mitochondria). In humans there are seven Sirtuins (SIRT1-7) that are implicated in various physiological processes including aging and age-related disorders such as neoplasms, cardiovascular, metabolic and neurodegenerative diseases, and inflammation. Nowadays, the estimated life expectancy is definitely longer than in the past thus, we may consider all aging-related problems as having a strong social impact. Consequently, Sirtuins are emerging, particularly from a pharmacological point of view, as new and valuable drug targets.

Original languageEnglish
Pages (from-to)653-661
Number of pages9
JournalCurrent Drug Targets
Volume14
Issue number6
DOIs
Publication statusPublished - 2013

Keywords

  • Aging
  • Caloric restriction
  • Cancer
  • Deacetylase
  • Drug targets
  • NAD
  • X-ray crystallography

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine

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