Department of Toxicology, School of Public Health, Shandong University, 44 Wenhuaxi Road, Jinan, 250012, Shandong, People's Republic of China.
School of Public Health, Fujian Medical University, 1 Xueyuan Road, Fuzhou, 350108, Fujian, People's Republic of China.
Cell Mol Life Sci. 2018 Jul;75(13):2389-2406. doi: 10.1007/s00018-018-2812-1. Epub 2018 Apr 19.
Axon degeneration is a pathophysiological process of axonal dying and breakdown, which is characterized by several morphological features including the accumulation of axoplasmic organelles, disassembly of microtubules, and fragmentation of the axonal cytoskeleton. Autophagy, a highly conserved lysosomal-degradation machinery responsible for the control of cellular protein quality, is widely believed to be essential for the maintenance of axonal homeostasis in neurons. In recent years, more and more evidence suggests that dysfunctional autophagy is associated with axonal degeneration in many neurodegenerative diseases. Here, we review the core machinery of autophagy in neuronal cells, and provide several major steps that interfere with autophagy flux in neurodegenerative conditions. Furthermore, this review highlights the potential role of neuronal autophagy in axon degeneration, and presents some possible molecular mechanisms by which dysfunctional autophagy leads to axon degeneration in pathological conditions.
轴突变性是轴突死亡和崩溃的一种病理生理过程,其特征是几种形态特征,包括轴浆细胞器的积累、微管的解体和轴突细胞骨架的碎片化。自噬是一种高度保守的溶酶体降解机制,负责控制细胞蛋白质质量,被广泛认为对神经元中轴突的动态平衡至关重要。近年来,越来越多的证据表明,自噬功能障碍与许多神经退行性疾病中的轴突变性有关。在这里,我们回顾了神经元细胞中自噬的核心机制,并提供了几种在神经退行性疾病中干扰自噬流的主要步骤。此外,本综述强调了神经元自噬在轴突变性中的潜在作用,并提出了一些可能的分子机制,说明自噬功能障碍如何导致病理条件下的轴突变性。