Autophagic myelin destruction by schwann cells during wallerian degeneration and segmental demyelination

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• 作者：So Young Jang ; Yoon Kyung Shin ; So Young Park ; Joo Youn Park ; Hye Jeong Lee ; Young Hyun Yoo ; Jong Kuk Kim and Hwan Tae Park
• 关键词：autophagy ; lysosome ; conditional knockout ; inflammatory neuropathy ; dedifferentiation ; injury
• 刊名：Glia
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：64
• 期：5
• 页码：730-742
• 全文大小：1391K
• ISSN：1098-1136

文摘

As lysosomal hydrolysis has long been suggested to be responsible for myelin clearance after peripheral nerve injury, in this study, we investigated the possible role of autophagolysosome formation in myelin phagocytosis by Schwann cells and its final contribution to nerve regeneration. We found that the canonical formation of autophagolysosomes was induced in demyelinating Schwann cells after injury, and the inhibition of autophagy via Schwann cell-specific knockout of the atg7 gene or pharmacological intervention of lysosomal function caused a significant delay in myelin clearance. However, Schwann cell dedifferentiation, as demonstrated by extracellular signal-regulated kinase activation and c-Jun induction, and redifferentiation were not significantly affected, and thus the entire repair program progressed normally in atg7 knockout mice. Finally, autophagic Schwann cells were also found during segmental demyelination in a mouse model of inflammatory peripheral neuropathy. Together, our findings suggest that autophagy is the self-myelin destruction mechanism of Schwann cells, but mechanistically, it is a process distinct from Schwann cell plasticity for nerve repair. GLIA 2016;64:730–742