Alzheimer's disease (AD) is a chronic and progressive neurological brain disorder. AD pathophysiology is mainly represented by formation of neuritic plaques and neurofibrillary tangles (NFTs). Neuritic plaques are made up of amyloid beta (Aβ) peptides, which play a central role in AD pathogenesis. In AD brain, Aβ peptide accumulates due to overproduction, insufficient clearance and defective proteolytic degradation. The degradation and cleavage mechanism of Aβ peptides by several human enzymes have been discussed previously. In the mean time, numerous experimental and bioinformatics reports indicated the significance of microbial enzymes having potential to degrade Aβ peptides. Thus, there is a need to shift the focus toward the substrate specificity and structure-function relationship of Aβ peptide-degrading microbial enzymes. Hence, in this review, we discussed in vitro and in silico studies of microbial enzymes viz. cysteine protease and zinc metallopeptidases having ability to degrade Aβ peptides. In silico study showed that cysteine protease can cleave Aβ peptide between Lys16-Cys17; similarly, several other enzymes also showed capability to degrade Aβ peptide at different sites. Thus, this review paves the way to explore the role of microbial enzymes in Aβ peptide degradation and to design new lead compounds for AD treatment.

中文翻译：

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淀粉样β肽降解微生物酶及其在药物设计中的意义。

阿尔茨海默病（AD）是一种慢性进行性神经性脑部疾病。AD病理生理学主要表现为神经炎斑和神经原纤维缠结（NFT）的形成。神经炎斑块由 β 淀粉样蛋白 (Aβ) 肽组成，在 AD 发病机制中发挥着核心作用。在 AD 大脑中，Aβ 肽由于产生过量、清除不足和蛋白水解降解缺陷而积聚。之前已经讨论过几种人类酶对 Aβ 肽的降解和切割机制。与此同时，大量的实验和生物信息学报告表明微生物酶具有降解 Aβ 肽的潜力。因此，需要将焦点转向Aβ肽降解微生物酶的底物特异性和结构功能关系。因此，在这篇综述中，我们讨论了微生物酶的体外和计算机研究。具有降解 Aβ 肽能力的半胱氨酸蛋白酶和锌金属肽酶。计算机研究表明，半胱氨酸蛋白酶可以切割 Lys16-Cys17 之间的 Aβ 肽；同样，其他几种酶也表现出在不同位点降解 Aβ 肽的能力。因此，本综述为探索微生物酶在 Aβ 肽降解中的作用以及设计用于 AD 治疗的新先导化合物铺平了道路。