title: Sirtuin functions and modulation: from chemistry to the clinic.
abstract: Sirtuins are NAD(+)-dependent histone deacetylases regulating important metabolic pathways in prokaryotes and eukaryotes and are involved in many biological processes such as cell survival, senescence, proliferation, apoptosis, DNA repair, cell metabolism, and caloric restriction. The seven members of this family of enzymes are considered potential targets for the treatment of human pathologies including neurodegenerative diseases, cardiovascular diseases, and cancer. Furthermore, recent interest focusing on sirtuin modulators as epigenetic players in the regulation of fundamental biological pathways has prompted increased efforts to discover new small molecules able to modify sirtuin activity. Here, we review the role, mechanism of action, and biological function of the seven sirtuins, as well as their inhibitors and activators.
authors.affiliation: Dipartimento di Biochimica, Biofisica e Patologia Generale, Seconda Università degli Studi di Napoli, Vico L. De Crecchio 7, 80138 Napoli, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Carafa
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" Università di Roma, 00185 Roma, Italy.
authors.forename: Dante
authors.initials: D
authors.lastname: Rotili
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" Università di Roma, 00185 Roma, Italy.|Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Viale Regina Elena, 291, 00161 Roma, Italy.
authors.forename: Mariantonietta
authors.initials: M
authors.lastname: Forgione
authors.affiliation: Dipartimento di Biochimica, Biofisica e Patologia Generale, Seconda Università degli Studi di Napoli, Vico L. De Crecchio 7, 80138 Napoli, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cuomo
authors.affiliation: Dipartimento di Biochimica, Biofisica e Patologia Generale, Seconda Università degli Studi di Napoli, Vico L. De Crecchio 7, 80138 Napoli, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Serretiello
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" Università di Roma, 00185 Roma, Italy.
authors.forename: Gebremedhin Solomon
authors.initials: GS
authors.lastname: Hailu
authors.affiliation: School of Pharmacy, University of Eastern Finland, FI-70210 Kuopio, Finland.
authors.forename: Elina
authors.initials: E
authors.lastname: Jarho
authors.affiliation: School of Pharmacy, University of Eastern Finland, FI-70210 Kuopio, Finland.
authors.forename: Maija
authors.initials: M
authors.lastname: Lahtela-Kakkonen
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" Università di Roma, 00185 Roma, Italy.|Istituto Pasteur, Fondazione Cenci-Bolognetti, "Sapienza" Università di Roma, 00185 Roma, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Mai
authors.affiliation: Dipartimento di Biochimica, Biofisica e Patologia Generale, Seconda Università degli Studi di Napoli, Vico L. De Crecchio 7, 80138 Napoli, Italy.|Istituto di Genetica e Biofisica, Via P. Castellino 111, 80131 Napoli, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Altucci
mesh_terms: D049109:Cell Proliferation; D002470:Cell Survival; D016922:Cellular Senescence; D004260:DNA Repair; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D037761:Sirtuins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D037761:Sirtuins
keywords: Cancer; Drug discovery; Epigenetics; Neurodegeneration; SIRT modulators; Sirtuins