Mitochondrial dysfunction and intracellular calcium dysregulation in ALS.
Mitochondrial dysfunction and intracellular calcium dysregulation in ALS.
复制标题
DOI：
10.1016/j.mad.2010.05.003
复制
发表时间：
2010-07
影响因子：
5.3
通讯作者：
Manfredi, Giovanni
中科院分区：
文献类型：
--
作者：
Kawamata, Hibiki;Manfredi, Giovanni
肌萎缩侧索硬化症（ALS）是一种影响老年人的破坏性神经退行性疾病。脊髓和大脑中运动神经元的逐渐丧失导致肌肉麻痹和死亡。与其他常见的神经退行性疾病一样，衰老相关的线粒体功能障碍越来越多地被认为是致病因素之一。线粒体对细胞存活至关重要：它们为细胞提供能量，缓冲细胞内钙，并调节凋亡性细胞死亡。线粒体异常是否是神经退行性过程的触发因素或结果，以及线粒体功能障碍导致疾病的机制尚不清楚。钙稳态是神经元中线粒体的主要功能，并且有充分的证据表明ALS中细胞内钙失调。线粒体功能障碍对细胞内钙稳态的影响及其在运动神经元死亡中的作用是值得深入讨论的有趣问题。显然，解开线粒体功能障碍，钙失调和神经元死亡之间的因果关系是理解ALS发病机制的关键。在这篇综述中，我们将概述ALS中线粒体功能障碍的各个方面的现有知识，特别强调这些异常对细胞内钙处理的作用。
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder that affects the aging population. A progressive loss of motor neurons in the spinal cord and brain leads to muscle paralysis and death. As in other common neurodegenerative diseases, aging-related mitochondrial dysfunction is increasingly being considered among the pathogenic factors. Mitochondria are critical for cell survival: they provide energy to the cell, buffer intracellular calcium, and regulate apoptotic cell death. Whether mitochondrial abnormalities are a trigger or a consequence of the neurodegenerative process and the mechanisms whereby mitochondrial dysfunction contributes to disease are not clear yet. Calcium homeostasis is a major function of mitochondria in neurons, and there is ample evidence that intracellular calcium is dysregulated in ALS. The impact of mitochondrial dysfunction on intracellular calcium homeostasis and its role in motor neuron demise are intriguing issues that warrants in depth discussion. Clearly, unraveling the causal relationship between mitochondrial dysfunction, calcium dysregulation, and neuronal death is critical for the understanding of ALS pathogenesis. In this review, we will outline the current knowledge of various aspects of mitochondrial dysfunction in ALS, with a special emphasis on the role of these abnormalities on intracellular calcium handling.
登录
查看更多内容
影响因子：
4.7
作者：
Bilsland, Lynsey G.;Nirmalananthan, Niranjanan;Duchen, Michael R.
通讯作者：
Duchen, Michael R.
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：
5.3
作者：
Cassina, Patricia;Cassina, Adriana;Radi, Rafael
通讯作者：
Radi, Rafael
影响因子：
64.8
作者：
Baines, CP;Kaiser, RA;Molkentin, JD
通讯作者：
Molkentin, JD
影响因子：
4.8
作者：
Dupuis, L;di Scala, F;Loeffler, JP
通讯作者：
Loeffler, JP