The endosomal-lysosomal system: from acidification and cargo sorting to neurodegeneration.
The endosomal-lysosomal system: from acidification and cargo sorting to neurodegeneration.
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DOI：
10.1186/s40035-015-0041-1
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发表时间：
2015
影响因子：
12.6
通讯作者：
Wang G
中科院分区：
文献类型：
--
作者：
Hu YB;Dammer EB;Ren RJ;Wang G
内体-溶酶体系统由一组动态相互转化的细胞内膜区室组成，其包括早期内体、再循环内体、晚期内体和溶酶体。此外，自噬体执行自噬，其将细胞内内容物递送至溶酶体。内体和/或自噬体成熟为溶酶体在细胞内产生了独特的酸性环境，用于蛋白水解和将不需要的细胞组分再循环为可用的氨基酸和其他生物分子结构单元。在内吞途径中，内体逐渐成熟为溶酶体和晚期内体的酸化伴随着囊泡运输、蛋白质分选和一些分选货物的靶向降解。两个相反的分选系统在这些过程中运行：运输所需的内体分选复合物（ESCRT）支持靶向降解，逆转录酶支持某些货物的逆行检索。内体-溶酶体系统正在成为许多神经退行性疾病的核心参与者，表现出可能在发病机制和可行的治疗策略中揭示的潜在作用。在这里，我们专注于内吞途径沿着内体-溶酶体成熟，酸化和分选系统的生理过程，并进一步讨论内体-溶酶体系统异常与神经退行性疾病，特别是阿尔茨海默病（AD）之间的关系。
The endosomal-lysosomal system is made up of a set of intracellular membranous compartments that dynamically interconvert, which is comprised of early endosomes, recycling endosomes, late endosomes, and the lysosome. In addition, autophagosomes execute autophagy, which delivers intracellular contents to the lysosome. Maturation of endosomes and/or autophagosomes into a lysosome creates an unique acidic environment within the cell for proteolysis and recycling of unneeded cellular components into usable amino acids and other biomolecular building blocks. In the endocytic pathway, gradual maturation of endosomes into a lysosome and acidification of the late endosome are accompanied by vesicle trafficking, protein sorting and targeted degradation of some sorted cargo. Two opposing sorting systems are operating in these processes: the endosomal sorting complex required for transport (ESCRT) supports targeted degradation and the retromer supports retrograde retrieval of certain cargo. The endosomal-lysosomal system is emerging as a central player in a host of neurodegenerative diseases, demonstrating potential roles which are likely to be revealed in pathogenesis and for viable therapeutic strategies. Here we focus on the physiological process of endosomal-lysosomal maturation, acidification and sorting systems along the endocytic pathway, and further discuss relationships between abnormalities in the endosomal-lysosomal system and neurodegenerative diseases, especially Alzheimer’s disease (AD).