After decades of research and clinical trials there is still no cure for Alzheimer’s disease (AD). While impaired clearance of amyloid beta (Aβ) peptides is considered as one of the major causes of AD, it was recently complemented by a potential role of other toxic amyloidogenic species. Insulin-degrading enzyme (IDE) is the proteolytic culprit of various β-forming peptides, both extracellular and intracellular. On the basis of demonstrated allosteric activation of IDE against Aβ, it is possible to propose a new strategy for the targeted IDE-based cleansing of different toxic aggregation-prone peptides. Consequently, specific allosteric activation of IDE coupled with state-of-the-art compound delivery and CRISP-Cas9 technique of transgene insertion can be instrumental in the fight against AD and related neurodegenerative maladies.

经过数十年的研究和临床试验，仍然无法治愈阿尔茨海默氏病（AD）。虽然淀粉样蛋白β（Aβ）肽清除能力受损被认为是AD的主要原因之一，但最近它被其他有毒淀粉样蛋白物种的潜在作用所弥补。胰岛素降解酶（IDE）是细胞外和细胞内各种β形成肽的蛋白水解元凶。基于IDE对Aβ的变构活化作用，有可能提出一种新的策略，针对不同的有毒聚集倾向的肽进行有针对性的基于IDE的清洗。因此，IDE的特异变构激活结合最新的化合物递送和转基因插入的CRISP-Cas9技术可在对抗AD和相关的神经退行性疾病中发挥作用。