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

[101] Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1 [J].

Rodgers, JT ;

Lerin, C ;

Haas, W ;

Gygi, SP ;

Spiegelman, BM ;

Puigserver, P .

NATURE, 2005, 434 (7029) :113-118

[102] Sir2 mediates longevity in the fly through a pathway related to calorie restriction [J].

Rogina, B ;

Helfand, SL .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (45) :15998-16003

[103] Longevity regulation by Drosophila Rpd3 deacetylase and caloric restriction [J].

Rogina, B ;

Helfand, SL ;

Frankel, S .

SCIENCE, 2002, 298 (5599) :1745-1745

[104] The human silent information regulator NO homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase [J].

Schwer, B ;

North, BJ ;

Frye, RA ;

Ott, M ;

Verdin, E .

JOURNAL OF CELL BIOLOGY, 2002, 158 (04) :647-657

[105] Ribosomal Protein S6 Kinase 1 Signaling Regulates Mammalian Life Span [J].

Selman, Colin ;

Tullet, Jennifer M. A. ;

Wieser, Daniela ;

Irvine, Elaine ;

Lingard, Steven J. ;

Choudhury, Agharul I. ;

Claret, Marc ;

Al-Qassab, Hind ;

Carmignac, Danielle ;

Ramadani, Faruk ;

Woods, Angela ;

Robinson, Iain C. A. ;

Schuster, Eugene ;

Batterham, Rachel L. ;

Kozma, Sara C. ;

Thomas, George ;

Carling, David ;

Okkenhaug, Klaus ;

Thornton, Janet M. ;

Partridge, Linda ;

Gems, David ;

Withers, Dominic J. .

SCIENCE, 2009, 326 (5949) :140-144

[106] SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes [J].

Shi, T ;

Wang, F ;

Stieren, E ;

Tong, Q .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (14) :13560-13567

[107] Obesity and the regulation of energy balance [J].

Spiegelman, BM ;

Flier, JS .

CELL, 2001, 104 (04) :531-543

[108] SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B [J].

Sun, Cheng ;

Zhang, Fang ;

Ge, Xinjian ;

Yan, Tingting ;

Chen, Xingmiao ;

Shi, Xianglin ;

Zhai, Qiwei .

CELL METABOLISM, 2007, 6 (04) :307-319

[109] Nucleocytoplasmic shuttling of the NAD+-dependent histone deacrtylase SIRT1 [J].

Tanno, Masaya ;

Sakamoto, Jun ;

Miura, Tetsuji ;

Shimamoto, Kazuaki ;

Horio, Yoshiyuki .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (09) :6823-6832

[110] Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans [J].

Tissenbaum, HA ;

Guarente, L .

NATURE, 2001, 410 (6825) :227-230

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