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自噬及其对神经退行性疾病的影响：TDP-43和C9orf72的新作用

Autophagy and Its Impact on Neurodegenerative Diseases: New Roles for TDP-43 and C9orf72.

作者信息

Budini Mauricio, Buratti Emanuele, Morselli Eugenia, Criollo Alfredo

机构信息

Dentistry Faculty, Institute in Dentistry Sciences, University of ChileSantiago, Chile.

International Centre for Genetic Engineering and BiotechnologyTrieste, Italy.

出版信息

Front Mol Neurosci. 2017 May 30;10:170. doi: 10.3389/fnmol.2017.00170. eCollection 2017.

DOI:10.3389/fnmol.2017.00170
PMID:28611593
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5447761/
Abstract

Autophagy is a catabolic mechanism where intracellular material is degraded by vesicular structures called autophagolysosomes. Autophagy is necessary to maintain the normal function of the central nervous system (CNS), avoiding the accumulation of misfolded and aggregated proteins. Consistently, impaired autophagy has been associated with the pathogenesis of various neurodegenerative diseases. The proteins TAR DNA-binding protein-43 (TDP-43), which regulates RNA processing at different levels, and chromosome 9 open reading frame 72 (C9orf72), probably involved in membrane trafficking, are crucial in the development of neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD). Additionally, recent studies have identified a role for these proteins in the control of autophagy. In this manuscript, we review what is known regarding the autophagic mechanism and discuss the involvement of TDP-43 and C9orf72 in autophagy and their impact on neurodegenerative diseases.

摘要

自噬是一种分解代谢机制，细胞内物质通过称为自噬溶酶体的囊泡结构进行降解。自噬对于维持中枢神经系统（CNS）的正常功能至关重要，可避免错误折叠和聚集蛋白的积累。一致的是，自噬受损与多种神经退行性疾病的发病机制相关。蛋白质TAR DNA结合蛋白43（TDP - 43）在不同水平调节RNA加工，以及9号染色体开放阅读框72（C9orf72）可能参与膜运输，在肌萎缩侧索硬化症（ALS）和额颞叶痴呆（FTLD）等神经退行性疾病的发展中起关键作用。此外，最近的研究已经确定了这些蛋白质在自噬控制中的作用。在本手稿中，我们回顾了关于自噬机制的已知内容，并讨论了TDP - 43和C9orf72在自噬中的作用及其对神经退行性疾病的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1163/5447761/873a319a9104/fnmol-10-00170-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1163/5447761/a588f811137d/fnmol-10-00170-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1163/5447761/aa0c090f56a4/fnmol-10-00170-g0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1163/5447761/aee19112f05a/fnmol-10-00170-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1163/5447761/1f12d543a7c6/fnmol-10-00170-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1163/5447761/a13b12dcf657/fnmol-10-00170-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1163/5447761/873a319a9104/fnmol-10-00170-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1163/5447761/a588f811137d/fnmol-10-00170-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1163/5447761/aa0c090f56a4/fnmol-10-00170-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1163/5447761/4a7da9e438c6/fnmol-10-00170-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1163/5447761/aee19112f05a/fnmol-10-00170-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1163/5447761/1f12d543a7c6/fnmol-10-00170-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1163/5447761/a13b12dcf657/fnmol-10-00170-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1163/5447761/873a319a9104/fnmol-10-00170-g0007.jpg

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