Section on Nervous System Development and Plasticity and.
Section on Intracellular Protein Trafficking, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
J Neurosci. 2020 Jan 8;40(2):256-266. doi: 10.1523/JNEUROSCI.1066-19.2019. Epub 2019 Nov 19.
Autophagy is the cellular process involved in transportation and degradation of membrane, proteins, pathogens, and organelles. This fundamental cellular process is vital in development, plasticity, and response to disease and injury. Compared with neurons, little information is available on autophagy in glia, but it is paramount for glia to perform their critical responses to nervous system disease and injury, including active tissue remodeling and phagocytosis. In myelinating glia, autophagy has expanded roles, particularly in phagocytosis of mature myelin and in generating the vast amounts of membrane proteins and lipids that must be transported to form new myelin. Notably, autophagy plays important roles in removing excess cytoplasm to promote myelin compaction and development of oligodendrocytes, as well as in remyelination by Schwann cells after nerve trauma. This review summarizes the cell biology of autophagy, detailing the major pathways and proteins involved, as well as the roles of autophagy in Schwann cells and oligodendrocytes in development, plasticity, and diseases in which myelin is affected. This includes traumatic brain injury, Alexander's disease, Alzheimer's disease, hypoxia, multiple sclerosis, hereditary spastic paraplegia, and others. Promising areas for future research are highlighted.
自噬是一种涉及膜、蛋白质、病原体和细胞器运输和降解的细胞过程。这种基本的细胞过程对于发育、可塑性以及对疾病和损伤的反应至关重要。与神经元相比，关于神经胶质细胞中的自噬，人们了解甚少，但神经胶质细胞对于对神经系统疾病和损伤做出关键反应至关重要，包括主动的组织重塑和吞噬作用。在髓鞘形成的神经胶质细胞中，自噬具有扩展的作用，特别是在吞噬成熟的髓鞘和生成大量的膜蛋白和脂质方面，这些必须运输到形成新的髓鞘。值得注意的是，自噬在去除多余的细胞质以促进髓鞘的压缩和少突胶质细胞的发育，以及施万细胞在神经损伤后的髓鞘修复中起着重要作用。本综述总结了自噬的细胞生物学，详细介绍了涉及的主要途径和蛋白质，以及自噬在施万细胞和少突胶质细胞发育、可塑性以及髓鞘受影响的疾病中的作用。这包括创伤性脑损伤、亚历山大病、阿尔茨海默病、缺氧、多发性硬化症、遗传性痉挛性截瘫等。强调了未来研究的有前景的领域。
