Su Kimmy G, Banker Gary, Bourdette Dennis, Forte Michael
Oregon Health & Science University, Vollum Institute, L474, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA.
Curr Neurol Neurosci Rep. 2009 Sep;9(5):411-7. doi: 10.1007/s11910-009-0060-3.
Multiple sclerosis (MS) is a chronic disease of the central nervous system, affecting more than 2 million people worldwide. Traditionally considered an inflammatory demyelinating disease, recent evidence now points to axonal degeneration as crucial to the development of irreversible disability. Studies show that axonal degeneration occurs throughout the entire course of MS. Although the specific mechanisms causing axonal damage may differ at various stages, mitochondrial failure seems to be a common underlying theme. This review addresses the mitochondrial hypothesis for axonal degeneration in MS, highlighting the mechanisms by which mitochondrial dysfunction leads to axonal disruption in acute inflammatory lesions and the chronic axonopathy in progressive MS. Emphasis is placed on Ca(2+), free radical production, and permeability transition pore opening as key players in mitochondrial failure, axonal transport impairment, and subsequent axonal degeneration. In addition, the role of mitochondria as therapeutic targets for neuroprotection in MS is addressed.
多发性硬化症（MS）是一种中枢神经系统的慢性疾病，全球有超过200万人受其影响。传统上被认为是一种炎症性脱髓鞘疾病，而最近的证据表明轴突退变对于不可逆残疾的发展至关重要。研究表明，轴突退变发生在MS的整个病程中。尽管在不同阶段导致轴突损伤的具体机制可能有所不同，但线粒体功能障碍似乎是一个共同的潜在主题。本综述探讨了MS中轴突退变的线粒体假说，强调了线粒体功能障碍导致急性炎症性病变中轴突破坏以及进展性MS中慢性轴索性神经病变的机制。重点关注钙离子（Ca(2+)）、自由基产生和通透性转换孔开放，它们是线粒体功能障碍、轴突运输受损及随后轴突退变的关键因素。此外，还讨论了线粒体作为MS神经保护治疗靶点的作用。
