Targeting Insulin-Degrading Enzyme to Treat Type 2 Diabetes Mellitus.
Targeting Insulin-Degrading Enzyme to Treat Type 2 Diabetes Mellitus.
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DOI：
10.1016/j.tem.2015.11.003
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Tang WJ
中科院分区：
文献类型：
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作者：
Tang WJ
胰岛素降解酶 (IDE) 选择性降解形成有毒聚集体的肽，例如胰岛素、胰岛淀粉样多肽和 β 淀粉样蛋白 (Aβ)，以维持蛋白质稳态。 IDE 缺陷与 2 型糖尿病 (T2DM) 和阿尔茨海默病 (AD) 的发生有关。结构和生化分析揭示了 IDE 介导的淀粉样肽破坏的分子基础，并且该信息已被用来开发有前景的 IDE 抑制剂，以改善葡萄糖稳态。然而，IDE 的抑制也会导致葡萄糖不耐受。本综述重点关注我们对 IDE 结构和功能的理解以及 IDE 抑制剂的发现的最新进展，以及开发基于 IDE 的人类疾病（特别是 T2DM）疗法的挑战。
Insulin degrading enzyme (IDE) selectively degrades peptides such as insulin, amylin, and amyloid β (Aβ) that form toxic aggregates, to maintain proteostasis. IDE defects are linked to the development of type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD). Structural and biochemical analyses revealed the molecular basis for IDE-mediated destruction of amyloidogenic peptides and this information has been exploited to develop promising inhibitors of IDE to improve glucose homeostasis. However, the inhibition of IDE can also lead to glucose intolerance. This review focuses on recent advances regarding our understanding of the structure and function of IDE and the discovery of IDE inhibitor, as well as challenges in developing IDE-based therapy for human diseases, particularly T2DM.