The emerging therapeutic potential of sirtuin-interacting drugs: from cell death to lifespan extension

被引：154

作者：

Porcu, M ^{[1
]}

Chiarugi, A ^{[1
]}

机构：

[1] Univ Florence, Dept Preclin & Clin Pharmacol, I-50139 Florence, Italy

来源：

TRENDS IN PHARMACOLOGICAL SCIENCES | 2005年 / 26卷 / 02期

关键词：

D O I：

10.1016/j.tips.2004.12.009

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Acetylation of chromatin-interacting proteins is central to the epigenetic regulation of genome architecture and gene expression. Chemicals that modulate the acetylation of nuclear proteins have proved instrumental in experimental models of several human diseases. Sirtuins represent a new class of evolutionary conserved histone deacetylases, originally identified in yeast, that have emerging pathogenetic roles in cancer, diabetes, muscle differentiation, heart failure, neurodegeneration and aging. In this article, we focus on sirtuins and provide an appraisal of current compounds that either activate or inhibit sirtuin activity, highlighting their therapeutic potential for the treatment of human diseases.

引用

页码：94 / 103

页数：10

共 79 条

[1] 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

[2] Yeast life-span extension by calorie restriction is independent of NAD fluctuation [J].

Anderson, RM ;

Latorre-Esteves, M ;

Neves, AR ;

Lavu, S ;

Medvedik, O ;

Taylor, C ;

Howitz, KT ;

Santos, H ;

Sinclair, DA .

SCIENCE, 2003, 302 (5653) :2124-2126

[3] Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae [J].

Anderson, RM ;

Bitterman, KJ ;

Wood, JG ;

Medvedik, O ;

Sinclair, DA .

NATURE, 2003, 423 (6936) :181-185

[4] Manipulation of a nuclear NAD+ salvage pathway delays aging without altering steady-state NAD+ levels [J].

Anderson, RM ;

Bitterman, KJ ;

Wood, JG ;

Medvedik, O ;

Cohen, H ;

Lin, SS ;

Manchester, JK ;

Gordon, JI ;

Sinclair, DA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (21) :18881-18890

[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] Structural basis for the mechanism and regulation of Sir2 enzymes [J].

Avalos, JL ;

Boeke, JD ;

Wolberger, C .

MOLECULAR CELL, 2004, 13 (05) :639-648

[7] Human histone deacetylase SIRT2 interacts with the homeobox transcription factor HOXA10 [J].

Bae, NS ;

Swanson, MJ ;

Vassilev, A ;

Howard, BH .

JOURNAL OF BIOCHEMISTRY, 2004, 135 (06) :695-700

[8] Identification of a small molecule inhibitor of Sir2p [J].

Bedalov, A ;

Gatbonton, T ;

Irvine, WP ;

Gottschling, DE ;

Simon, JA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (26) :15113-15118

[9] Acetylation inactivates the transcriptional repressor BCL6 [J].

Bereshchenko, OR ;

Gu, W ;

Dalla-Favera, R .

NATURE GENETICS, 2002, 32 (04) :606-613

[10] The new life of a centenarian:: signalling functions of NAD(P) [J].

Berger, F ;

Ramírez-Hernández, MH ;

Ziegler, M .

TRENDS IN BIOCHEMICAL SCIENCES, 2004, 29 (03) :111-118

← 1 2 3 4 5 6 7 8 →