Pharmacological manipulations of CNS sirtuins: Potential effects on metabolic homeostasis

被引：7

作者：

Ramadori, Giorgio ^{[1
]}

Coppari, Roberto ^{[1
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Hypothalam Res, Dallas, TX 75390 USA

来源：

PHARMACOLOGICAL RESEARCH | 2010年 / 62卷 / 01期

关键词：

Brain; Sirtuins; Metabolism; Homeostasis; Pharmaceutical; Metabolic-sensor proteins; RESTRICTION-INDUCED LONGEVITY; FOXO TRANSCRIPTION FACTORS; NAD-DEPENDENT DEACETYLASE; SMALL-MOLECULE ACTIVATORS; PANCREATIC BETA-CELLS; EXTENDS LIFE-SPAN; CALORIE RESTRICTION; KAPPA-B; GLUCOSE-HOMEOSTASIS; SIRT1; DEACETYLASE;

D O I：

10.1016/j.phrs.2010.02.002

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Sirtuins are deacetylases and/or mono-ADP-ribosyltransferases found in organisms ranging from bacteria to humans. These enzymes use oxidized nicotinamide adenine dinucleotide (NAD(+)) and a long array of different proteins (e.g.: histones, transcription factors, cofactors, members of the electron transport chain, etc.) as substrates. Sirtuins-mediated reactions yield deacetylated proteins, nicotinamide (NAM) and 2'-O-acetyl-ADP-ribose (O-AADPr) or mono-ADP-ribosylated proteins and NAM. As these post-translational modifications change the activity of their targets and sirtuins depend on NAD(+) to function, these enzymes are thought to link metabolic statuses with cellular gene expression, activity and fate; as such sirtuins are thought to be bona fide metabolic-sensor proteins. Due to their diverse targets, sirtuins affect metabolism, senescence, longevity, circadian rhythms and many other biological and physiological programs. In this review we focus on their known roles on metabolic homeostasis with particular emphasis on their functions in neurons within the central nervous system (CNS). We also touch upon the possible metabolic outcomes of pharmacological manipulations of CNS sirtuins. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：48 / 54

页数：7

共 123 条

[11] Therapeutic potential of resveratrol:: the in vivo evidence [J].

Baur, Joseph A. ;

Sinclair, David A. .

NATURE REVIEWS DRUG DISCOVERY, 2006, 5 (06) :493-506

[12]

BEHER DWUJ, 2009, CHEM BIOL DRUG DESIG

[13] Liver X Receptors (LXR) as Therapeutic Targets in Dyslipidemia [J].

Beltowski, Jerzy .

CARDIOVASCULAR THERAPEUTICS, 2008, 26 (04) :297-316

[14]

Bhakar AL, 2002, J NEUROSCI, V22, P8466

[15] Two neurons mediate diet-restriction-induced longevity in C-elegans [J].

Bishop, Nicholas A. ;

Guarente, Leonard .

NATURE, 2007, 447 (7144) :545-+

[16] Mechanism of human SIRT1 activation by resveratrol [J].

Borra, MT ;

Smith, BC ;

Denu, JM .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (17) :17187-17195

[17] Ligand activation of LXRβ reverses atherosclerosis and cellular cholesterol overload in mice lacking LXRα and apoE [J].

Bradley, Michelle N. ;

Hong, Cynthia ;

Chen, Mingyi ;

Joseph, Sean B. ;

Wilpitz, Damien C. ;

Wang, Xuping ;

Lusis, Aldons J. ;

Collins, Allan ;

Hseuh, Willa A. ;

Collins, Jon L. ;

Tangirala, Rajendra K. ;

Tontonoz, Peter .

JOURNAL OF CLINICAL INVESTIGATION, 2007, 117 (08) :2337-2346

[18] The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor [J].

Brown, MS ;

Goldstein, JL .

CELL, 1997, 89 (03) :331-340

[19] 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

[20] Hypothalamic Sirt1 Regulates Food Intake in a Rodent Model System [J].

Cakir, Isin ;

Perello, Mario ;

Lansari, Omar ;

Messier, Norma J. ;

Vaslet, Charles A. ;

Nillni, Eduardo A. .

PLOS ONE, 2009, 4 (12)

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