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首页> 外文期刊>Alzheimer s Research & Therapy >Regulation of distinct pools of amyloid β-protein by multiple cellular proteases
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Regulation of distinct pools of amyloid β-protein by multiple cellular proteases

机译：多种细胞蛋白酶对淀粉样β蛋白不同库的调节

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摘要

Alzheimer’s disease (AD) is a progressive, age-related neurodegenerative disorder characterized by extracellular and intracellular deposition of the amyloid β-protein (Aβ). The study of rare, familial forms of AD has shown that sustained elevations in the production of Aβ (either all forms or specific pathogenic variants thereof) are sufficient to trigger the full spectrum of cognitive and histopathological features of the disease. Although the exact cause or causes remain unknown, emerging evidence suggests that impairments in the clearance of Aβ, after it is produced, may underlie the vast majority of sporadic AD cases. This review focuses on Aβ-degrading proteases (AβDPs), which have emerged as particularly important mediators of Aβ clearance. A wide variety of proteases that – by virtue of their particular regional and subcellular localization profiles – define distinct pools of Aβ have been identified. Different pools of Aβ, in turn, may contribute differentially to the pathogenesis of the disease. The study of individual AβDPs, therefore, promises to offer new insights into the mechanistic basis of AD pathogenesis and, ultimately, may facilitate the development of effective methods for its prevention or treatment or both.
机译：阿尔茨海默氏病（AD）是一种与年龄相关的进行性神经退行性疾病，其特征在于淀粉样β蛋白（Aβ）的细胞外和细胞内沉积。对罕见的家族性AD的研究表明，Aβ产生的持续升高（所有形式或其特定的致病变体）足以触发该疾病的全部认知和组织病理学特征。尽管确切的原因仍然未知，但新出现的证据表明，Aβ清除后的清除障碍可能是绝大多数散发性AD病例的基础。这篇综述着重于降解Aβ的蛋白酶（AβDPs），它已成为Aβ清除的特别重要的媒介。已经发现了各种各样的蛋白酶，这些蛋白酶凭借其特定的区域和亚细胞定位特性，可以定义不同的Aβ库。反过来，不同的Aβ库可能会对该疾病的发病机制做出不同的贡献。因此，对单个AβDPs的研究有望为AD发病机理的机械基础提供新的见解，并最终可能促进其预防或治疗或两者的有效方法的发展。

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