Sirtuin functions and modulation: from chemistry to the clinic

被引：301

作者：

Carafa, Vincenzo ^{[1
]}

Rotili, Dante ^{[2
]}

Forgione, Mariantonietta ^{[2
,3
]}

Cuomo, Francesca ^{[1
]}

Serretiello, Enrica ^{[1
]}

Hailu, Gebremedhin Solomon ^{[2
]}

Jarho, Elina ^{[4
]}

Lahtela-Kakkonen, Maija ^{[4
]}

Mai, Antonello ^{[2
,5
]}

Altucci, Lucia ^{[1
,6
]}

机构：

[1] Univ Naples 2, Dipartimento Biochim Biofis & Patol Gen, Vico L De Crecchio 7, I-80138 Naples, Italy

[2] Univ Roma La Sapienza, Dipartimento Chim & Tecnol Farmaco, Piazzale Aldo Moro 5, I-00185 Rome, Italy

[3] Ist Italiano Tecnol, Ctr Life Nano Sci Sapienza, Viale Regina Elena 291, I-00161 Rome, Italy

[4] Univ Eastern Finland, Sch Pharm, FI-70210 Kuopio, Finland

[5] Univ Roma La Sapienza, Fdn Cenci Bolognetti, Ist Pasteur, I-00185 Rome, Italy

[6] Ist Genet & Biofis, Via P Castellino 111, I-80131 Naples, Italy

来源：

CLINICAL EPIGENETICS | 2016年 / 8卷

关键词：

Epigenetics; Sirtuins; SIRT modulators; Drug discovery; Cancer; Neurodegeneration; EPSILON-THIOACETYL-LYSINE; SMALL-MOLECULE ACTIVATORS; CANCER STEM-CELLS; CALORIC RESTRICTION; TUMOR-SUPPRESSOR; ACETYL-LYSINE; LIFE-SPAN; ANTIPROLIFERATIVE PROPERTIES; PSEUDOPEPTIDIC INHIBITORS; ALLOSTERIC ACTIVATORS;

D O I：

10.1186/s13148-016-0224-3

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Sirtuins are NAD(+)-dependent histone deacetylases regulating important metabolic pathways in prokaryotes and eukaryotes and are involved in many biological processes such as cell survival, senescence, proliferation, apoptosis, DNA repair, cell metabolism, and caloric restriction. The seven members of this family of enzymes are considered potential targets for the treatment of human pathologies including neurodegenerative diseases, cardiovascular diseases, and cancer. Furthermore, recent interest focusing on sirtuin modulators as epigenetic players in the regulation of fundamental biological pathways has prompted increased efforts to discover new small molecules able to modify sirtuin activity. Here, we review the role, mechanism of action, and biological function of the seven sirtuins, as well as their inhibitors and activators.

引用

页数：21

共 119 条

[1] Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration [J].

Araki, T ;

Sasaki, Y ;

Milbrandt, J .

SCIENCE, 2004, 305 (5686) :1010-1013

[2] Inhibition of Human Sirtuins by in Situ Generation of an Acetylated Lysine-ADP-Ribose Conjugate [J].

Asaba, Tomomi ;

Suzuki, Takayoshi ;

Ueda, Rie ;

Tsumoto, Hiroki ;

Nakagawa, Hidehiko ;

Miyata, Naoki .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2009, 131 (20) :6989-6996

[3] SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation [J].

Barber, Matthew F. ;

Michishita-Kioi, Eriko ;

Xi, Yuanxin ;

Tasselli, Luisa ;

Kioi, Mitomu ;

Moqtaderi, Zarmik ;

Tennen, Ruth I. ;

Paredes, Silvana ;

Young, Nicolas L. ;

Chen, Kaifu ;

Struhl, Kevin ;

Garcia, Benjamin A. ;

Gozani, Or ;

Li, Wei ;

Chua, Katrin F. .

NATURE, 2012, 487 (7405) :114-+

[4] 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

[5] 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

[6] Discovery of oxazolo[4,5-b]pyridines and related heterocyclic analogs as novel SIRT1 activators [J].

Bemis, Jean E. ;

Vu, Chi B. ;

Xie, Roger ;

Nunes, Joseph J. ;

Ng, Pui Yee ;

Disch, Jeremy S. ;

Milne, Jill C. ;

Carney, David P. ;

Lynch, Amy V. ;

Jin, Lei ;

Smith, Jesse J. ;

Lavu, Siva ;

Iffland, Andre ;

Jirousek, Michael R. ;

Perni, Robert B. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (08) :2350-2353

[7] Substrate specificity and kinetic mechanism of the Sir2 family of NAD+-dependent histone/protein deacetylases [J].

Borra, MT ;

Langer, MR ;

Slama, JT ;

Denu, JM .

BIOCHEMISTRY, 2004, 43 (30) :9877-9887

[8]

Bosch-Presegue Laia, 2011, Genes Cancer, V2, P648, DOI 10.1177/1947601911417862

[9] Sirtuins and disease: the road ahead [J].

Carafa, Vincenzo ;

Nebbioso, Angela ;

Altucci, Lucia .

FRONTIERS IN PHARMACOLOGY, 2012, 3

[10] High levels of SIRT1 expression enhance tumorigenesis and associate with a poor prognosis of colorectal carcinoma patients [J].

Chen, Xiaojing ;

Sun, Kai ;

Jiao, Shufan ;

Cai, Ning ;

Zhao, Xue ;

Zou, Hanbing ;

Xie, Yuexia ;

Wang, Zhengshi ;

Zhong, Ming ;

Wei, Lixin .

SCIENTIFIC REPORTS, 2014, 4

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