Cecilie Vogt Klinik, Charité - University Hospital Berlin, Germany.
Exp Neurol. 2010 Sep;225(1):9-17. doi: 10.1016/j.expneurol.2009.11.019. Epub 2009 Dec 1.
Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, in which the myelin sheath has been considered to be the primary target for many years. However, an increasing number of reports have focused on neurodegenerative aspects of the disease pathogenesis. Recent studies in post-mortem MS biopsies and in the animal model Experimental Autoimmune Encephalomyelitis (EAE) have shown that key features of neurodegeneration, i.e. axonal transection, neuronal cell atrophy and neuronal death already occur in early disease phases. Furthermore, it has become clear that irreversible disability correlates stronger with the neuronal affectation than with demyelination. However the cause of neuronal damage still remains elusive, since both demyelination-dependent and direct immune cell-mediated mechanisms have been suggested so far. Here, we summarize the current concepts and recently identified molecular mechanisms of inflammatory neurodegeneration in autoimmune CNS inflammation and highlight the role of different immune cells in the complex network of interactions leading to neuronal damage.
多发性硬化症（MS）是一种中枢神经系统的慢性炎症性脱髓鞘疾病，多年来，髓鞘一直被认为是许多疾病的主要靶点。然而，越来越多的报道关注疾病发病机制中的神经退行性方面。最近在多发性硬化症死后活检和实验性自身免疫性脑脊髓炎（EAE）动物模型中的研究表明，神经退行性的关键特征，即轴突横断、神经元细胞萎缩和神经元死亡，已经在疾病的早期阶段发生。此外，已经很清楚，不可逆的残疾与神经元损伤的相关性比脱髓鞘更强。然而，神经元损伤的原因仍然难以捉摸，因为迄今为止已经提出了依赖脱髓鞘和直接免疫细胞介导的机制。在这里，我们总结了自身免疫性中枢神经系统炎症中炎症性神经退行性变的当前概念和最近确定的分子机制，并强调了不同免疫细胞在导致神经元损伤的复杂相互作用网络中的作用。
