Mitochondrial dysfunction in amyotrophic lateral sclerosis.
Mitochondrial dysfunction in amyotrophic lateral sclerosis.
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DOI：
10.1016/j.bbadis.2009.08.012
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发表时间：
2010-01
影响因子：
6.2
通讯作者：
Zhu, Haining
中科院分区：
文献类型：
--
作者：
Shi, Ping;Gal, Jozsef;Kwinter, David M.;Liu, Xiaoyan;Zhu, Haining
关键词：
肌萎缩侧索硬化症(ALS)运动神经元变性的病因尚不清楚。根据对ALS患者和转基因动物模型的研究，ALS可能是一种多因素和多系统的疾病。ALS的发病机制有多种，如氧化应激、谷氨酸兴奋毒性、线粒体损伤、轴突运输缺陷、胶质细胞病理和RNA代谢异常等。线粒体在兴奋毒性、细胞凋亡和细胞存活中起着关键作用，已被证明是ALS发病机制中的早期靶点，并有助于疾病的进展。在过度表达突变SOD1的人类患者和ALS小鼠中，都发现了线粒体的形态和功能缺陷。突变的SOD1被发现优先与线粒体相关，继而损害线粒体的功能。最近的研究表明，ALS患者线粒体沿微管的轴突运输和线粒体动力学也可能受到干扰。这些结果也说明了在轴突和神经肌肉连接中维持适当的线粒体功能的关键重要性，支持了ALS新兴的“垂死性”轴索病模型。在这篇综述中，我们将讨论线粒体功能障碍是如何与SOD1的ALS变体联系在一起的，以及线粒体损伤在疾病病因中的作用机制。
The etiology of motor neuron degeneration in amyotrophic lateral sclerosis (ALS) remains to be better understood. Based on the studies from ALS patients and transgenic animal models, it is believed that ALS is likely to be a multifactorial and multisystem disease. Many mechanisms have been postulated to be involved in the pathology of ALS, such as oxidative stress, glutamate excitotoxicity, mitochondrial damage, defective axonal transport, glia cell pathology and aberrant RNA metabolism. Mitochondria, which play crucial roles in excitotoxicity, apoptosis and cell survival, have shown to be an early target in ALS pathogenesis and contribute to the disease progression. Morphological and functional defects in mitochondria were found in both human patients and ALS mice overexpressing mutant SOD1. Mutant SOD1 was found to be preferentially associated with mitochondria and subsequently impair mitochondrial function. Recent studies suggest that axonal transport of mitochondria along microtubules and mitochondrial dynamics may also be disrupted in ALS. These results also illustrate the critical importance of maintaining proper mitochondrial function in axons and neuromuscular junctions, supporting the emerging “dying-back” axonopathy model of ALS. In this review, we will discuss how mitochondrial dysfunction has been linked to the ALS variants of SOD1 and the mechanisms by which mitochondrial damage contributes to the disease etiology.
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影响因子：
5.3
作者：
Fischer, LR;Culver, DG;Glass, JD
通讯作者：
Glass, JD
DOI：
10.1083/jcb.200601067
发表时间：
2006-05-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Glater EE;Megeath LJ;Stowers RS;Schwarz TL
通讯作者：
Schwarz TL
DOI：
10.1073/pnas.0605814103
发表时间：
2006-09-12
影响因子：
11.1
作者：
Ferri, Alberto;Cozzolino, Mauro;Carri, Maria Teresa
通讯作者：
Carri, Maria Teresa
影响因子：
6.1
作者：
Dewil, Maarten;dela Cruz, Vidal F.;Robberecht, Wim
通讯作者：
Robberecht, Wim
影响因子：
3.7
作者：
Dupuis L;Gonzalez de Aguilar JL;Echaniz-Laguna A;Eschbach J;Rene F;Oudart H;Halter B;Huze C;Schaeffer L;Bouillaud F;Loeffler JP
通讯作者：
Loeffler JP