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神经元自噬和轴突变性。

Neuronal autophagy and axon degeneration.

机构信息

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.

出版信息

Cell Mol Life Sci. 2018 Jul;75(13):2389-2406. doi: 10.1007/s00018-018-2812-1. Epub 2018 Apr 19.

DOI:10.1007/s00018-018-2812-1
PMID:29675785
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11105516/
Abstract

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.

摘要

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。

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本文引用的文献

1
Neuronal Mitophagy in Neurodegenerative Diseases.神经退行性疾病中的神经元线粒体自噬
Front Mol Neurosci. 2017 Mar 8;10:64. doi: 10.3389/fnmol.2017.00064. eCollection 2017.
2
The SARM1 Toll/Interleukin-1 Receptor Domain Possesses Intrinsic NAD Cleavage Activity that Promotes Pathological Axonal Degeneration.SARM1 Toll/白细胞介素-1受体结构域具有内在的NAD裂解活性,可促进病理性轴突退变。
Neuron. 2017 Mar 22;93(6):1334-1343.e5. doi: 10.1016/j.neuron.2017.02.022.
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Defective retrograde transport impairs autophagic clearance in Alzheimer disease neurons.逆行运输缺陷会损害阿尔茨海默病神经元中的自噬清除作用。
Autophagy. 2017 May 4;13(5):982-984. doi: 10.1080/15548627.2017.1291114. Epub 2017 Feb 28.
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Death Receptor 6 Promotes Wallerian Degeneration in Peripheral Axons.死亡受体 6 促进周围轴突的瓦勒变性。
Curr Biol. 2017 Mar 20;27(6):890-896. doi: 10.1016/j.cub.2017.01.062. Epub 2017 Mar 9.
5
HMGB1 Mediates Autophagy Dysfunction via Perturbing Beclin1-Vps34 Complex in Dopaminergic Cell Model.在多巴胺能细胞模型中,高迁移率族蛋白B1通过扰乱Beclin1-Vps34复合物介导自噬功能障碍。
Front Mol Neurosci. 2017 Jan 31;10:13. doi: 10.3389/fnmol.2017.00013. eCollection 2017.
6
Mitophagy and Alzheimer's Disease: Cellular and Molecular Mechanisms.线粒体自噬与阿尔茨海默病:细胞和分子机制
Trends Neurosci. 2017 Mar;40(3):151-166. doi: 10.1016/j.tins.2017.01.002. Epub 2017 Feb 9.
7
Autophagy Receptors and Neurodegenerative Diseases.自噬受体与神经退行性疾病。
Trends Cell Biol. 2017 Jul;27(7):491-504. doi: 10.1016/j.tcb.2017.01.001. Epub 2017 Feb 3.
8
Axon degeneration induces glial responses through Draper-TRAF4-JNK signalling.轴突变性通过 Draper-TRAF4-JNK 信号诱导神经胶质反应。
Nat Commun. 2017 Feb 6;8:14355. doi: 10.1038/ncomms14355.
9
MAPK signaling promotes axonal degeneration by speeding the turnover of the axonal maintenance factor NMNAT2.丝裂原活化蛋白激酶(MAPK)信号传导通过加速轴突维持因子烟酰胺单核苷酸腺苷转移酶2(NMNAT2)的周转来促进轴突变性。
Elife. 2017 Jan 17;6:e22540. doi: 10.7554/eLife.22540.
10
GSK3B-mediated phosphorylation of MCL1 regulates axonal autophagy to promote Wallerian degeneration.糖原合成酶激酶3β介导的MCL1磷酸化调节轴突自噬以促进沃勒变性。
J Cell Biol. 2017 Feb;216(2):477-493. doi: 10.1083/jcb.201606020. Epub 2017 Jan 4.