Research Group Neurodegeneration, KULAK, Etienne Sabbelaan 53, 8500, Kortrijk, Belgium.
J Bioenerg Biomembr. 2011 Dec;43(6):587-92. doi: 10.1007/s10863-011-9393-0.
A growing body of evidence suggests that mitochondrial dysfunctions play a crucial role in the pathogenesis of various neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting both upper and lower motor neurons. Although ALS is predominantly a sporadic disease, approximately 10% of cases are familial. The most frequent familial form is caused by mutations in the gene encoding Cu/Zn superoxide dismutase 1 (SOD1). A dominant toxic gain of function of mutant SOD1 has been considered as the cause of the disease and mitochondria are thought to be key players in the pathogenesis. However, the exact nature of the link between mutant SOD1 and mitochondrial dysfunctions remains to be established. Here, we briefly review the evidence for mitochondrial dysfunctions in familial ALS and discuss a possible link between mutant SOD1 and mitochondrial dysfunction.
越来越多的证据表明，线粒体功能障碍在各种神经退行性疾病的发病机制中起着关键作用，包括肌萎缩侧索硬化症（ALS），这是一种影响上下运动神经元的神经退行性疾病。尽管 ALS 主要是一种散发性疾病，但约有 10%的病例是家族性的。最常见的家族性形式是由编码铜/锌超氧化物歧化酶 1（SOD1）的基因突变引起的。突变 SOD1 的显性毒性功能获得被认为是疾病的原因，线粒体被认为是发病机制中的关键因素。然而，突变 SOD1 与线粒体功能障碍之间的确切联系仍有待确定。在这里，我们简要回顾了家族性 ALS 中线粒体功能障碍的证据，并讨论了突变 SOD1 与线粒体功能障碍之间可能存在的联系。
