AMPK allostery: A therapeutic target for the management/treatment of diabetic nephropathy

被引:25
作者
Ayinde, Kehinde Sulaimon [1 ]
Olaoba, Olamide Tosin [2 ]
Ibrahim, Boyenle [3 ]
Lei, Du [4 ]
Lu, Qian [4 ]
Yin, Xiaoxing [4 ]
Adelusi, Temitope Isaac [3 ,4 ]
机构
[1] Univ Estadual Campinas, Inst Biol, Campinas, SP, Brazil
[2] Univ Fed Sao Carlos, Lab Funct & Struct Biochem, Sao Carlos, SP, Brazil
[3] Ladoke Akintola Univ Technol, Dept Biochem, Computat Biol Drug Discovery Lab, Ogbomosho, Nigeria
[4] Xuzhou Med Univ, Jiangsu Key Lab New Drug Res & Clin Pharm, Xuzhou 221004, Jiangsu, Peoples R China
关键词
AMPK; DN; Hyperglycemia; Oxidative stress; Allosteric regulation; ACTIVATED PROTEIN-KINASE; GLYCATION END-PRODUCTS; FATTY-ACID OXIDATION; SKELETAL-MUSCLE; STRUCTURAL BASIS; KIDNEY-DISEASE; ENERGY-SENSOR; MAMMALIAN TARGET; UPSTREAM KINASE; KEY REGULATOR;
D O I
10.1016/j.lfs.2020.118455
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Diabetic nephropathy (DN) is a chronic complication of diabetes mellitus (DM) with approximately 30-40% of patients with DM developing nephropathy, and it is the leading cause of end-stage renal diseases and diabetic morbidity. The pathogenesis of DN is primarily associated with irregularities in the metabolism of glucose and lipid leading to hyperglycemia-induced oxidative stress, which has been a major target together with blood pressure regulation in the control of DN progression. However, the regulation of 5' adenosine monophosphate-activated protein kinase (AMPK), a highly conserved protein kinase for maintaining energy balance and cellular growth and repair has been implicated in the development of DM and its complications. Therefore, targeting AMPK pathway has been explored as a therapeutic strategy for the treatment of diabetes and its complication, although most of the mechanisms have not been fully elucidated. In this review, we discuss the structure of AMPK relevant to understanding its allosteric regulation and its role in the pathogenesis and progression of DN. We also identify therapeutic agents that modulate AMPK and its downstream targets with their specific mechanisms of action in the treatment of DN.
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页数:15
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