Center for Dementia Research, Nathan S. Kline Institute, Orangeburg, New York 10962, USA.
Cold Spring Harb Perspect Biol. 2012 Oct 1;4(10):a008839. doi: 10.1101/cshperspect.a008839.
Autophagy is implicated in the pathogenesis of major neurodegenerative disorders although concepts about how it influences these diseases are still evolving. Once proposed to be mainly an alternative cell death pathway, autophagy is now widely viewed as both a vital homeostatic mechanism in healthy cells and as an important cytoprotective response mobilized in the face of aging- and disease-related metabolic challenges. In Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and other diseases, impairment at different stages of autophagy leads to the buildup of pathogenic proteins and damaged organelles, while defeating autophagy's crucial prosurvival and antiapoptotic effects on neurons. The differences in the location of defects within the autophagy pathway and their molecular basis influence the pattern and pace of neuronal cell death in the various neurological disorders. Future therapeutic strategies for these disorders will be guided in part by understanding the manifold impact of autophagy disruption on neurodegenerative diseases.
自噬与多种主要神经退行性疾病的发病机制有关，尽管目前对于自噬如何影响这些疾病的概念仍在不断发展。自噬曾一度被认为主要是一种细胞死亡的替代途径，而现在被广泛认为是健康细胞中一种重要的动态平衡机制，也是在面对与衰老和疾病相关的代谢挑战时被动员起来的重要细胞保护反应。在阿尔茨海默病、帕金森病、亨廷顿病、肌萎缩侧索硬化症和其他疾病中，自噬在不同阶段的损伤导致致病性蛋白和受损细胞器的积累，而破坏自噬对神经元的关键生存和抗细胞凋亡作用。自噬途径中缺陷的位置差异及其分子基础影响了各种神经退行性疾病中神经元细胞死亡的模式和速度。对自噬破坏对神经退行性疾病的多方面影响的理解，将在一定程度上指导这些疾病的未来治疗策略。
