AMP-Activated Protein Kinase: A Target for Drugs both Ancient and Modern

被引：313

作者：

Hardie, D. Grahame ^{[1
]}

Ross, Fiona A. ^{[1
]}

Hawley, Simon A. ^{[1
]}

机构：

[1] Univ Dundee, Coll Life Sci, Div Cell Signalling & Immunol, Dundee DD1 5EH, Scotland

来源：

CHEMISTRY & BIOLOGY | 2012年 / 19卷 / 10期

基金：

英国惠康基金;

关键词：

FATTY-ACID OXIDATION; RESPIRATORY COMPLEX-I; ENERGY SENSOR; RAT-LIVER; STRUCTURAL BASIS; SKELETAL-MUSCLE; METABOLIZING-ENZYMES; GLYCOGEN-SYNTHASE; LKB1-AMPK PATHWAY; UPSTREAM KINASE;

D O I：

10.1016/j.chembiol.2012.08.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. It is activated, by a mechanism requiring the tumor suppressor LKB1, by metabolic stresses that increase cellular ADP:ATP and/or AMP:ATP ratios. Once activated, it switches on catabolic pathways that generate ATP, while switching off biosynthetic pathways and cell-cycle progress. These effects suggest that AMPK activators might be useful for treatment and/or prevention of type 2 diabetes and cancer. Indeed, AMPK is activated by the drugs metformin and salicylate, the latter being the major breakdown product of aspirin. Metformin is widely used to treat diabetes, while there is epidemiological evidence that both metformin and aspirin provide protection against cancer. We review the mechanisms of AMPK activation by these and other drugs, and by natural products derived from traditional herbal medicines.

引用

页码：1222 / 1236

页数：15

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