Pathogenic cascades in lysosomal disease-Why so complex?
Pathogenic cascades in lysosomal disease-Why so complex?
复制标题
DOI：
10.1007/s10545-008-1040-5
复制
发表时间：
2009-04
影响因子：
4.2
通讯作者：
Walkley, S. U.
中科院分区：
文献类型：
--
作者：
Walkley, S. U.
溶酶体疾病代表了一大组超过50种临床公认的疾病，这些疾病是由影响溶酶体的细胞器的先天性代谢缺陷引起的。溶酶体是更大的内体/溶酶体系统的组成部分，并且与泛素-蛋白体和自噬体系统密切相关，它们共同构成了底物降解和再循环，稳态控制，以及信号。超过三分之二的溶酶体疾病影响大脑，神经元似乎特别容易受到溶酶体损害，并显示出从特定轴突和树突异常到神经元死亡的多种后果。虽然溶酶体功能的失败通常会导致溶酶体储存，但新的研究认为，溶酶体疾病也可以被适当地视为“缺乏状态”，而不仅仅是过剩（储存）。干扰信号传导事件和通常由内体/溶酶体系统控制的补救处理可能是解释溶酶体疾病固有复杂性的关键机制。溶酶体疾病发病机制的分析提供了一个独特的窗口，通过它来观察更大的溶酶体系统对正常细胞健康的重要性。
Lysosomal disease represents a large group of more than 50 clinically recognized conditions resulting from inborn errors of metabolism affecting the organelle known as the lysosome.The lysosome is an integral part of the larger endosomal/lysosomal system, and is closely allied with the ubiquitin-proteosomal and autophagosomal systems, which together comprise essential cell machinery for substrate degradation and recycling, homeostatic control, as well as signaling. More than two-thirds of lysosomal diseases affect the brain, with neurons appearing particularly vulnerable to lysosomal compromise and showing diverse consequences ranging from specific axonal and dendritic abnormalities to neuron death. While failure of lysosomal function characteristically leads to lysosomal storage, new studies argue that lysosomal diseases may also be appropriately viewed as “states of deficiency” rather than simply overabundance (storage). Interference with signaling events and salvage processing normally controlled by the endosomal/lysosomal system may represent key mechanisms accounting for the inherent complexity of lysosomal disorders. Analysis of lysosomal disease pathogenesis provides a unique window through which to observe the importance of the greater lysosomal system for normal cell health.
登录
查看更多内容
影响因子：
19
作者：
Pentchev, Peter G.;Blanchette-Mackie, E. Joan;Dawidowicz, Eliezar A.
通讯作者：
Dawidowicz, Eliezar A.
影响因子：
64.8
作者：
Passafaro, M;Nakagawa, T;Sheng, M
通讯作者：
Sheng, M
影响因子：
3.5
作者：
Pacheco, Chris D.;Kunkel, Robin;Lieberman, Andrew P.
通讯作者：
Lieberman, Andrew P.
影响因子：
64.8
作者：
Komatsu, Masaaki;Waguri, Satoshi;Tanaka, Keiji
通讯作者：
Tanaka, Keiji
影响因子：
4.8
作者：
Cao, Yi;Espinola, Janice A.;Cotman, Susan L.
通讯作者：
Cotman, Susan L.