Endoplasmic reticulum and mitochondria in diseases of motor and sensory neurons: a broken relationship?
Endoplasmic reticulum and mitochondria in diseases of motor and sensory neurons: a broken relationship?
复制标题
DOI：
10.1038/s41419-017-0125-1
复制
发表时间：
2018-02-28
影响因子：
9
通讯作者：
Schneider BL
中科院分区：
文献类型：
--
作者：
Bernard-Marissal N;Chrast R;Schneider BL
神经退行性疾病的最新进展表明，多种分子机制导致神经元的病理变化。这些改变中的很大一部分可能与内质网（ER）和线粒体功能障碍有关，影响脂质和蛋白质的代谢和分泌、钙稳态和能量产生。值得注意的是，这些细胞器在ER上的专门结构域相互作用，称为细胞相关膜（MAMs）。这些膜结构依赖于位于线粒体或ER界面处的几种蛋白质复合物的相互作用，并作为钙、代谢物和脂质的交换平台，这对两种细胞器的功能至关重要。此外，最近的证据表明MAMs也在线粒体动力学和自噬的控制中发挥作用。因此，MAMs开始成为连接神经退行性疾病中观察到的许多变化的关键因素。这篇综述将集中于MAMs在肌萎缩侧索硬化症（ALS）和遗传性运动和感觉神经病，特别是影响神经元的神经退行性疾病与长突出轴突的作用。我们将讨论MAM信号缺陷如何损害神经元钙稳态、线粒体动力学、内质网功能和自噬，最终导致轴突变性。还将描述MAM功能障碍在神经胶质细胞中的可能影响，其可能影响支持神经元和/或轴突的能力。最后，MAMs作为一个有趣的目标，旨在延缓或预防神经退行性变的治疗干预措施的发展可能发挥的作用将被强调。
Recent progress in the understanding of neurodegenerative diseases revealed that multiple molecular mechanisms contribute to pathological changes in neurons. A large fraction of these alterations can be linked to dysfunction in the endoplasmic reticulum (ER) and mitochondria, affecting metabolism and secretion of lipids and proteins, calcium homeostasis, and energy production. Remarkably, these organelles are interacting with each other at specialized domains on the ER called mitochondria-associated membranes (MAMs). These membrane structures rely on the interaction of several complexes of proteins localized either at the mitochondria or at the ER interface and serve as an exchange platform of calcium, metabolites, and lipids, which are critical for the function of both organelles. In addition, recent evidence indicates that MAMs also play a role in the control of mitochondria dynamics and autophagy. MAMs thus start to emerge as a key element connecting many changes observed in neurodegenerative diseases. This review will focus on the role of MAMs in amyotrophic lateral sclerosis (ALS) and hereditary motor and sensory neuropathy, two neurodegenerative diseases particularly affecting neurons with long projecting axons. We will discuss how defects in MAM signaling may impair neuronal calcium homeostasis, mitochondrial dynamics, ER function, and autophagy, leading eventually to axonal degeneration. The possible impact of MAM dysfunction in glial cells, which may affect the capacity to support neurons and/or axons, will also be described. Finally, the possible role of MAMs as an interesting target for development of therapeutic interventions aiming at delaying or preventing neurodegeneration will be highlighted.
登录
查看更多内容
影响因子：
13.6
作者：
Boyer, Olivia;Benoit, Genevieve;Antignac, Corinne
通讯作者：
Antignac, Corinne
DOI：
10.1083/jcb.200211046
发表时间：
2003-01-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen H;Detmer SA;Ewald AJ;Griffin EE;Fraser SE;Chan DC
通讯作者：
Chan DC
影响因子：
3.7
作者：
Cosson P;Marchetti A;Ravazzola M;Orci L
通讯作者：
Orci L
影响因子：
1.1
作者：
Azzedine, H.;Senderek, J.;Chrast, R.
通讯作者：
Chrast, R.
影响因子：
14.5
作者：
Bernard-Marissal, Nathalie;Medard, Jean-Jacques;Chrast, Roman
通讯作者：
Chrast, Roman