Rethinking lysosomes and lysosomal disease.
Rethinking lysosomes and lysosomal disease.
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重新思考溶酶体和溶酶体疾病。
DOI：
10.1016/j.neulet.2021.136155
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发表时间：
2021
影响因子：
2.5
通讯作者：
Walkley,StevenU
中科院分区：
文献类型：
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作者：
Walkley,StevenU
一个多世纪前，溶酶体贮积病被确认并定义为一类主要影响儿童的疾病，并引起全身性疾病，通常伴有严重的神经系统后果。自从它们被发现以来，对其原因的研究一直是我们不断扩大细胞生物学知识和溶酶体在细胞功能中发挥核心作用的重要推动力。今天，我们认识到超过50种所谓的贮积性疾病，其中大多数在基因、蛋白质和通路参与的水平上被理解，但在溶酶体功能缺陷如何导致脑部疾病方面，很少有完全明确的；更少的人拥有能够有效挽救大脑功能的治疗方法。重要的是，我们也认识到贮积性疾病本身不仅仅是一类溶酶体疾病，因为溶酶体系统及其内体、自噬体和回收流在许多神经发育和神经退行性疾病中也出现了越来越重要的作用。尽管这些复杂疾病的各个方面都面临着持续的挑战，正如本期《神经科学快报》特刊中关于溶酶体贮积病的这篇文章和其他文章所反映的那样，在理解有效治疗这些疾病方面取得的进展和承诺从未如此之大。
Lysosomal storage diseases were recognized and defined over a century ago as a class of disorders affecting mostly children and causing systemic disease often accompanied by major neurological consequences. Since their discovery, research focused on understanding their causes has been an important driver of our ever-expanding knowledge of cell biology and the central role that lysosomes play in cell function. Today we recognize over 50 so-called storage diseases, with most understood at the level of gene, protein and pathway involvement, but few fully clarified in terms of how the defective lysosomal function causes brain disease; even fewer have therapies that can effectively rescue brain function. Importantly, we also recognize that storage diseases are not simply a class of lysosomal disorders all by themselves, as increasingly a critical role for the greater lysosomal system with its endosomal, autophagosomal and salvage streams has also emerged in a host of neurodevelopmental and neurodegenerative diseases. Despite persistent challenges across all aspects of these complex disorders, and as reflected in this and other articles focused on lysosomal storage diseases in this special issue ofNeuroscience Letters, the progress and promise to both understandandeffectively treat these conditions has never been greater.