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腺苷单磷酸激活的蛋白激酶及其在分解代谢中的关键作用:结构、调节、生物学活性及药理学激活

Adenosine monophosphate-activated kinase and its key role in catabolism: structure, regulation, biological activity, and pharmacological activation.

作者信息

Krishan Sukriti, Richardson Des R, Sahni Sumit

机构信息

Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, University of Sydney, Sydney, New South Wales, Australia.

Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, University of Sydney, Sydney, New South Wales, Australia

出版信息

Mol Pharmacol. 2015;87(3):363-77. doi: 10.1124/mol.114.095810. Epub 2014 Nov 24.

Abstract

Adenosine monophosphate-activated protein kinase (AMPK) is a cellular energy sensor, which once activated, plays a role in several processes within the cell to restore energy homeostasis. The protein enhances catabolic pathways, such as β-oxidation and autophagy, to generate ATP, and inhibits anabolic processes that require energy, including fatty acid, cholesterol, and protein synthesis. Due to its key role in the regulation of critical cellular pathways, deregulation of AMPK is associated with the pathology of many diseases, including cancer, Wolff-Parkinson-White syndrome, neurodegenerative disorders, diabetes, and metabolic syndrome. In fact, AMPK is a target of some pharmacological agents implemented in the treatment of diabetes (metformin and thiazolidinediones) as well as other naturally derived products, such as berberine, which is used in traditional medicine. Due to its critical role in the cell and the pathology of several disorders, research into developing AMPK as a therapeutic target is becoming a burgeoning and exciting field of pharmacological research. A profound understanding of the regulation and activity of AMPK would enhance its development as a promising therapeutic target.

摘要

腺苷单磷酸激活的蛋白激酶(AMPK)是一种细胞能量传感器,一旦被激活,它就在细胞内的多个过程中发挥作用,以恢复能量稳态。该蛋白增强分解代谢途径,如β-氧化和自噬,以产生ATP,并抑制需要能量的合成代谢过程,包括脂肪酸、胆固醇和蛋白质合成。由于其在关键细胞途径调节中的关键作用,AMPK失调与许多疾病的病理过程相关,包括癌症、预激综合征、神经退行性疾病、糖尿病和代谢综合征。事实上,AMPK是一些用于治疗糖尿病的药物(二甲双胍和噻唑烷二酮类)以及其他天然产物(如传统医学中使用的黄连素)的靶点。由于其在细胞和多种疾病病理过程中的关键作用,将AMPK开发为治疗靶点的研究正成为一个新兴且令人兴奋的药理学研究领域。对AMPK的调节和活性有深入的了解将促进其作为一个有前景的治疗靶点的开发。

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