Sirtuins - novel therapeutic targets to treat age-associated diseases

被引:382
作者
Lavu, Siva [1 ]
Boss, Olivier [1 ]
Elliott, Peter J. [1 ]
Lambert, Philip D. [1 ]
机构
[1] Sirtris Pharmaceut GSK Co, Cambridge, MA 02139 USA
关键词
D O I
10.1038/nrd2665
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Sirtuins post-translationally modulate the function of many cellular proteins that undergo reversible acetylation-deacetylation cycles, affecting physiological responses that have implications for treating diseases of ageing. Potent small-molecule modulators of sirtuins have shown efficacy in preclinical models of metabolic, neurodegenerative and inflammatory diseases, and so hold promise for drug discovery efforts in multiple therapeutic areas. Here, we discuss current knowledge and data that strengthens sirtuins as a druggable set of enzymes for the treatment of age-associated diseases, including activation of SIRT1 in type 2 diabetes.
引用
收藏
页码:841 / 853
页数:13
相关论文
共 160 条
[1]   Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase [J].
Ahuja, Nidhi ;
Schwer, Bjoern ;
Carobbio, Stefania ;
Waltregny, David ;
North, Brian J. ;
Castronovo, Vincenzo ;
Maechler, Pierre ;
Verdin, Eric .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (46) :33583-33592
[2]   Sirt1 regulates aging and resistance to oxidative stress in the heart [J].
Alcendor, Ralph R. ;
Gao, Shumin ;
Zhai, Peiyong ;
Zablocki, Daniela ;
Holle, Eric ;
Yu, Xianzhong ;
Tian, Bin ;
Wagner, Thomas ;
Vatner, Stephen F. ;
Sadoshima, Junichi .
CIRCULATION RESEARCH, 2007, 100 (10) :1512-1521
[3]   Silent information regulator 2α, a longevity factor and class III histone deacetylase, is an essential endogenous apoptosis inhibitor in cardiac myocytes [J].
Alcendor, RR ;
Kirshenbaum, LA ;
Imai, S ;
Vatner, SF ;
Sadoshima, J .
CIRCULATION RESEARCH, 2004, 95 (10) :971-980
[4]   Comparative analysis of the effects of resveratrol in two apoptotic models:: Inhibition of complex I and potassium deprivation in cerebellar neurons [J].
Alvira, D. ;
Yeste-Velasco, M. ;
Folch, J. ;
Verdaguer, E. ;
Canudas, A. M. ;
Pallas, M. ;
Camins, A. .
NEUROSCIENCE, 2007, 147 (03) :746-756
[5]   Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration [J].
Araki, T ;
Sasaki, Y ;
Milbrandt, J .
SCIENCE, 2004, 305 (5686) :1010-1013
[6]   Transcriptional coactivator PGC-1α controls the energy state and contractile function of cardiac muscle [J].
Arany, Z ;
He, HM ;
Lin, JD ;
Hoyer, K ;
Handschin, C ;
Toka, O ;
Ahmad, F ;
Matsui, T ;
Chin, S ;
Wu, PH ;
Rybkin, II ;
Shelton, JM ;
Manieri, M ;
Cinti, S ;
Schoen, FJ ;
Bassel-Duby, R ;
Rosenzweig, A ;
Ingwall, JS ;
Spiegelman, BM .
CELL METABOLISM, 2005, 1 (04) :259-271
[7]   Resveratrol improves health and survival of mice on a high-calorie diet [J].
Baur, Joseph A. ;
Pearson, Kevin J. ;
Price, Nathan L. ;
Jamieson, Hamish A. ;
Lerin, Carles ;
Kalra, Avash ;
Prabhu, Vinayakumar V. ;
Allard, Joanne S. ;
Lopez-Lluch, Guillermo ;
Lewis, Kaitlyn ;
Pistell, Paul J. ;
Poosala, Suresh ;
Becker, Kevin G. ;
Boss, Olivier ;
Gwinn, Dana ;
Wang, Mingyi ;
Ramaswamy, Sharan ;
Fishbein, Kenneth W. ;
Spencer, Richard G. ;
Lakatta, Edward G. ;
Le Couteur, David ;
Shaw, Reuben J. ;
Navas, Placido ;
Puigserver, Pere ;
Ingram, Donald K. ;
de Cabo, Rafael ;
Sinclair, David A. .
NATURE, 2006, 444 (7117) :337-342
[8]   Cytogenetics and Molecular Genetics of Malignant Gliomas and Medulloblastoma [J].
Bigner, Sandra H. ;
Vogelstein, Bert .
BRAIN PATHOLOGY, 1990, 1 (01) :12-18
[9]   SirT1 Regulates Energy Metabolism and Response to Caloric Restriction in Mice [J].
Boily, Gino ;
Seifert, Erin L. ;
Bevilacqua, Lisa ;
He, Xiao Hong ;
Sabourin, Guillaume ;
Estey, Carmen ;
Moffat, Cynthia ;
Crawford, Sean ;
Saliba, Sarah ;
Jardine, Karen ;
Xuan, Jian ;
Evans, Meredith ;
Harper, Mary-Ellen ;
McBurney, Michael W. .
PLOS ONE, 2008, 3 (03)
[10]   Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic β cells [J].
Bordone, L ;
Motta, MC ;
Picard, F ;
Robinson, A ;
Jhala, US ;
Apfeld, J ;
McDonagh, T ;
Lemieux, M ;
McBurney, M ;
Szilvasi, A ;
Easlon, EJ ;
Lin, SJ ;
Guarente, L .
PLOS BIOLOGY, 2006, 4 (02) :210-220