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General Review Article

针对糖尿病和糖尿病并发症的AMPK：能量稳态，自噬和线粒体健康

卷 26, 期 27, 2019

页: [5207 - 5229] 页: 23

弟呕挨: 10.2174/0929867325666180406120051

价格: $65

摘要

腺苷5''-单磷酸激活蛋白激酶（AMPK）是一种关键的酶蛋白，参与将能量感应与代谢操作联系起来。它是一种由几种上游激酶激活的丝氨酸/苏氨酸激酶。 AMPK是一种异源三聚体蛋白复合物，受AMP，ADP和ATP变构调节。 AMPK在生命系统的各种组织中广泛表达，例如心脏，肾脏，肝脏，大脑和骨骼肌。因此，预期AMPK的功能失常会掩盖几种人类疾病，尤其是与代谢和线粒体功能障碍有关的疾病。 AMPK活化剂包括合成衍生物和几种天然产物，已发现在几种动物疾病模型中显示出治疗缓解作用。 AMP，5-氨基咪唑-4-羧酰胺核苷（AICA核苷）和A769662是AMPK的重要激活剂，对糖尿病和糖尿病并发症具有潜在的治疗重要性。 AMPK调节已显示出对糖尿病，心血管并发症和糖尿病性神经病的有益作用。 AMPK调节的主要作用，除了严格检查炎症过程，自噬和细胞凋亡外，还确保线粒体的健康运转和能量稳态。对AMP和AICAR的结构研究表明，游离氨基对AMPK刺激至关重要。据报道，通过对A-592107和其他几种相关化合物进行前导优化研究而得到的非核苷噻吩并吡啶酮化合物A769662通过激活AMPK对糖尿病及其并发症表现出有希望的作用。在发现A769662之后，已经报道了几种噻吩并吡啶酮，羟基联苯吡咯并吡啶酮作为AMPK调节剂。该综述将探讨这些类似物的结构-功能关系，以及在糖尿病和糖尿病并发症中靶向AMPK的前景。

关键词: 糖尿病，糖尿病并发症，AMPK，自噬，线粒体（AICA核糖苷），A769662。

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