The Centre for Clinical Brain Science, University of Edinburgh, Chancellor's Building, Edinburgh EH16 4SB, United Kingdom.
Cold Spring Harb Perspect Med. 2018 Oct 1;8(10):a028985. doi: 10.1101/cshperspect.a028985.
The neuron is the target of inflammatory demyelinating processes in multiple sclerosis (MS). In progressive MS, however, there is a gathering body of evidence indicating molecular changes within neuronal cell bodies. All of these molecular changes to intrinsic neurons converge on mitochondria, and the most reproduced change relates to mitochondrial respiratory chain complex deficiency. This compromise in the capacity to generate ATP in the neuronal cell body is coupled with an increased demand for energy by the demyelinated axon, which is particularly relevant to the long tracts such as corticospinal tracts with long projection axons. Recent work in our laboratory and that of our collaborators indicate limited reflection of the molecular changes that are intrinsic neurons in the experimental disease models. The mitochondrial changes within neuronal compartments are an under-recognized aspect of progressive MS and likely to offer novel targets for the improvement of neuronal function as well as neuroprotection.
神经元是多发性硬化症（MS）中炎症性脱髓鞘过程的靶标。然而，在进行性 MS 中，越来越多的证据表明神经元细胞体内存在分子变化。所有这些内在神经元的分子变化都集中在线粒体上，而最常见的变化与线粒体呼吸链复合物缺陷有关。这种神经元细胞体产生 ATP 的能力受损与脱髓鞘轴突对能量的需求增加有关，这与长束（如皮质脊髓束）的长投射轴突特别相关。我们实验室和合作者的最近研究表明，实验性疾病模型中内在神经元的分子变化反映有限。神经元隔室中的线粒体变化是进行性 MS 的一个未被充分认识的方面，可能为改善神经元功能和神经保护提供新的靶点。
