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

来源：

NATURE REVIEWS DRUG DISCOVERY | 2008年 / 7卷 / 10期

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

[11] SIRT1 transgenic mice show phenotypes resembling calorie restriction [J].

Bordone, Laura ;

Cohen, Dena ;

Robinson, Ashley ;

Motta, Maria Carla ;

van Veen, Ed ;

Czopik, Agnieszka ;

Steele, Andrew D. ;

Crowe, Hayley ;

Marmor, Stephen ;

Luo, Jianyuan ;

Gu, Wei ;

Guarente, Leonard .

AGING CELL, 2007, 6 (06) :759-767

[12] Effects of long-term treatment with resveratrol and subcutaneous and oral estradiol administration on pituitary function in rats [J].

Böttner, M ;

Christoffel, J ;

Jarry, H ;

Wuttke, W .

JOURNAL OF ENDOCRINOLOGY, 2006, 189 (01) :77-88

[13] Resveratrol acts as a mixed agonist/antagonist for estrogen receptors α and β [J].

Bowers, JL ;

Tyulmenkov, VV ;

Jernigan, SC ;

Klinge, CM .

ENDOCRINOLOGY, 2000, 141 (10) :3657-3667

[14] Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase [J].

Brunet, A ;

Sweeney, LB ;

Sturgill, JF ;

Chua, KF ;

Greer, PL ;

Lin, YX ;

Tran, H ;

Ross, SE ;

Mostoslavsky, R ;

Cohen, HY ;

Hu, LS ;

Cheng, HL ;

Jedrychowski, MP ;

Gygi, SP ;

Sinclair, DA ;

Alt, FW ;

Greenberg, ME .

SCIENCE, 2004, 303 (5666) :2011-2015

[15] How is mitochondrial biogenesis affected in mitochondrial disease? [J].

Chabi, B ;

Adhihetty, PJ ;

Ljubicic, V ;

Hood, DA .

MEDICINE AND SCIENCE IN SPORTS AND EXERCISE, 2005, 37 (12) :2102-2110

[16] Increase in activity during calorie restriction requires Sirt1 [J].

Chen, D ;

Steele, AD ;

Lindquist, S ;

Guarente, L .

SCIENCE, 2005, 310 (5754) :1641-1641

[17] Histone H2A.z is essential for cardiac myocyte hypertrophy but opposed by silent information regulator 2α [J].

Chen, Ieng-Yi ;

Lypowy, Jacqueline ;

Pain, Jayashree ;

Sayed, Danish ;

Grinberg, Stan ;

Alcendor, Ralph R. ;

Sadoshima, Junichi ;

Abdellatif, Maha .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (28) :19369-19377

[18] SIRT1 protects against microglia-dependent amyloid-β toxicity through inhibiting NF-κB signaling [J].

Chen, J ;

Zhou, YG ;

Mueller-Steiner, S ;

Chen, LF ;

Kwon, H ;

Yi, SL ;

Mucke, L ;

Li, G .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (48) :40364-40374

[19] Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses [J].

Chen, WY ;

Wang, DH ;

Yen, RWC ;

Luo, JY ;

Gu, W ;

Baylin, SB .

CELL, 2005, 123 (03) :437-448

[20] Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice [J].

Cheng, HL ;

Mostoslavsky, R ;

Saito, S ;

Manis, JP ;

Gu, YS ;

Patel, P ;

Bronson, R ;

Appella, E ;

Alt, FW ;

Chua, KF .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (19) :10794-10799

← 1 2 3 4 5 6 7 8 9 10 →