Pathogenic mechanisms in lysosomal disease: a reappraisal of the role of the lysosome.
Pathogenic mechanisms in lysosomal disease: a reappraisal of the role of the lysosome.
复制标题
溶酶体疾病的致病机制：溶酶体作用的重新评估。
DOI：
10.1111/j.1651-2227.2007.00202.x
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Walkley,StevenU
中科院分区：
文献类型：
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作者：
Walkley,StevenU
认为溶酶体只是代表来自细胞表面及其内部的聚合物分子的连续降解中的末端细胞器的观点导致了对溶酶体贮积病的性质和表征它们的致病级联的重大误解。因此，溶酶体储存体通常被认为是“惰性的”，主要通过正常细胞器的机械过度拥挤或通过其他非特异性方式导致普遍的细胞毒性来诱导细胞功能障碍和死亡。然而，对溶酶体及其组成蛋白的现代研究提供了证据，支持这些细胞器在细胞代谢中发挥更大的作用。与内体、自噬体和相关囊泡系统密切相关，大溶酶体系统可以被概念化为一个重要的回收中心，充当中央代谢协调员，影响着细胞的各个方面，从信号转导到基因表达的调节。 结论：这种关于溶酶体在细胞中的作用的更广泛的观点不仅提供了对单基因缺陷如何影响的见解 对溶酶体功能的影响可能会导致这些疾病特有的大量复杂的细胞转化，但也表明新的和创新的疗法可能为改善疾病进展带来巨大的希望。
The view that lysosomes simply represent end organelles in the serial degradation of polymeric molecules derived from the cell surface and its interior has led to major misconceptions about the nature of lysosomal storage diseases and the pathogenic cascades that characterize them. Accordingly, lysosomal storage bodies are often considered ‘inert’, inducing cell dysfunction and death primarily through mechanical overcrowding of normal organelles or by other non‐specific means leading to generalized cytotoxicity. However, modern studies of lysosomes and their component proteins provide evidence to support a far greater role for these organelles in cell metabolism. In intimate association with endosomal, autophagosomal and related vesicular systems, the greater lysosomal system can be conceptualized as a vital recycling centre that serves as a central metabolic coordinator, influencing literally every aspect of the cell, from signal transduction to regulation of gene expression.Conclusion: This broader view of the role of lysosomes in cells not only provides insight into how single gene defects impacting on lysosomal function can result in the plethora of complex cellular transformations characteristic of these diseases, but also suggests new and innovative therapies that may hold considerable promise for ameliorating disease progression.