Department of Developmental and Molecular Biology, Marion Bessin Liver Research Center and Institute for Aging Studies, Albert Einstein College of Medicine, Bronx, New York, USA.
Nat Neurosci. 2010 Jul;13(7):805-11. doi: 10.1038/nn.2575.
Autophagy is essential for neuronal homeostasis, and its dysfunction has been directly linked to a growing number of neurodegenerative disorders. The reasons behind autophagic failure in degenerating neurons can be very diverse because of the different steps required for autophagy and the characterization of the molecular players involved in each of them. Understanding the step(s) affected in the autophagic process in each disorder could explain differences in the course of these pathologies and will be essential to developing targeted therapeutic approaches for each disease based on modulation of autophagy. Here we present examples of different types of autophagic dysfunction described in common neurodegenerative disorders and discuss the prospect of exploring some of the recently identified autophagic variants and the interactions among autophagic and non-autophagic proteolytic systems as possible future therapeutic targets.
自噬对于神经元的稳态至关重要,其功能障碍与越来越多的神经退行性疾病直接相关。由于自噬所需的不同步骤以及参与其中的分子成分的特征各不相同,退化神经元中自噬失败的原因可能多种多样。了解每种疾病的自噬过程中受影响的步骤,可以解释这些病理的过程中的差异,并对于基于自噬调节开发针对每种疾病的靶向治疗方法至关重要。在这里,我们列举了在常见神经退行性疾病中描述的不同类型的自噬功能障碍的实例,并讨论了探索一些最近发现的自噬变体以及自噬和非自噬蛋白水解系统之间的相互作用作为可能的未来治疗靶点的前景。