Sirtuin activators and inhibitors.
Sirtuins 1-7 (SIRT1-7) belong to the third class of deacetylase enzymes, which are dependent on NAD(+)  for activity. Sirtuins activity is linked to gene repression, metabolic control, apoptosis and cell survival, DNA repair, development, inflammation, neuroprotection, and healthy aging. Because sirtuins modulation could have beneficial effects on human diseases there is a growing interest in the discovery of small molecules modifying their activities. We review here those compounds known to activate or inhibit sirtuins, discussing the data that support the use of sirtuin-based therapies. Almost all sirtuin activators have been described only for SIRT1. Resveratrol is a natural compound which activates SIRT1, and may help in the treatment or prevention of obesity, and in preventing tumorigenesis and the aging-related decline in heart function and neuronal loss. Due to its poor bioavailability, reformulated versions of resveratrol with improved bioavailability have been developed (resVida, Longevinex(®) , SRT501). Molecules that are structurally unrelated to resveratrol (SRT1720, SRT2104, SRT2379, among others) have been also developed to stimulate sirtuin activities more potently than resveratrol. Sirtuin inhibitors with a wide range of core structures have been identified for SIRT1, SIRT2, SIRT3 and SIRT5 (splitomicin, sirtinol, AGK2, cambinol, suramin, tenovin, salermide, among others). SIRT1 inhibition has been proposed in the treatment of cancer, immunodeficiency virus infections, Fragile X mental retardation syndrome and for preventing or treating parasitic diseases, whereas SIRT2 inhibitors might be useful for the treatment of cancer and neurodegenerative diseases.
Departamento de Biología Celular, Fisiología e Inmunología, Campus Universitario de Rabanales, Edificio Severo Ochoa, Universidad de Córdoba, Campus de Excelencia Internacional Agroalimentario, Córdoba, Spain.
José M
JM
Villalba
Francisco J
FJ
Alcaín
D000975:Antioxidants / Q000737:chemistry* / Q000627:therapeutic use; D020536:Enzyme Activators / Q000737:chemistry* / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000627:therapeutic use; D005600:Fragile X Syndrome / Q000188:drug therapy / Q000201:enzymology; D006678:HIV / Q000187:drug effects / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy / Q000201:enzymology; D006801:Humans; D009284:Naphthols / Q000737:chemistry* / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000201:enzymology; D009765:Obesity / Q000188:drug therapy / Q000201:enzymology; D037761:Sirtuins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013267:Stilbenes / Q000737:chemistry* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D000975:Antioxidants; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D009284:Naphthols; D013267:Stilbenes; D037761:Sirtuins