Monash Immunology and Stem Cell Laboratories, Monash University, Clayton Victoria, Australia.
J Neuropathol Exp Neurol. 2010 Apr;69(4):323-34. doi: 10.1097/NEN.0b013e3181d60ddb.
Multiple sclerosis (MS) is a devastating neurological condition that mainly affects young adults and is associated with long-standing morbidity. The pathophysiology of MS is believed to involve immune-mediated multifocal lesions in the CNS that are characterized by inflammation, demyelination, and axonal injury. Most research efforts to date have concentrated on the mechanisms of immune-mediated demyelination, whereas mechanisms of axonal injury, the major determinant of neurological deficits in MS patients, have been elusive beyond observational analyses. This review discusses current understanding of the pathology and novel clinical investigations of axonal injury in MS and the commonly used MS animal model, experimental autoimmune encephalomyelitis. The review focuses on the etiology and the induction of axonal degeneration through molecular signaling cascades downstream of myelin-associated inhibitory factors. Defining and eventually elucidating the signaling pathways elicited during the onset and progression of MS may provide novel therapeutic strategies to limit axonal degeneration in the acute phase of the disease. Furthermore, blocking or potentiating specific signaling pathways, particularly those that mediate axon retraction and promote disassembly of the tubulin network, may promote regrowth of damaged axons in CNS regions affected by many acute and chronic disease processes.
多发性硬化症（MS）是一种破坏性的神经系统疾病，主要影响年轻人，并与长期发病有关。MS 的病理生理学被认为涉及中枢神经系统中的免疫介导的多灶性病变，其特征为炎症、脱髓鞘和轴突损伤。迄今为止，大多数研究工作都集中在免疫介导的脱髓鞘机制上，而轴突损伤的机制，即 MS 患者神经功能缺损的主要决定因素，除了观察性分析之外，仍然难以捉摸。这篇综述讨论了 MS 中轴突损伤的病理和新的临床研究以及常用的 MS 动物模型——实验性自身免疫性脑脊髓炎的当前认识。该综述重点介绍了通过髓鞘相关抑制因子下游的分子信号级联反应诱导轴突变性的病因和诱导。定义并最终阐明 MS 发作和进展过程中引发的信号通路可能为限制疾病急性期的轴突变性提供新的治疗策略。此外，阻断或增强特定的信号通路，特别是那些介导轴突回缩和促进微管网络解体的信号通路，可能会促进受许多急性和慢性疾病过程影响的中枢神经系统区域受损轴突的再生。
