Loeb Jeffrey A
Department of Neurology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Neurology. 2007 May 29;68(22 Suppl 3):S38-42; discussion S43-54. doi: 10.1212/01.wnl.0000275231.97764.43.
Based on the efficacy of immunomodulatory therapies in patients with multiple sclerosis (MS), much of the research and thinking about pathogenesis and treatment has traditionally focused on suppressing the immune system. Whatever the cause, recent studies have rekindled the notion that neurologic dysfunction in patients with MS relates best to the degree of neuronal (axonal) and glial damage. Therefore, as a means to understand the pathogenesis of MS and to develop biologically targeted new therapeutics, a greater understanding of axoglial biology is needed. Central to axoglial biology are protein regulatory factors that include gliotrophic factors such as the neuregulins and neurotrophic factors that communicate between these cell types and are critical for nervous system development. Unfortunately, the track record of neurotrophic factors for treating other neurologic disorders has not been impressive, in part because of a failure to aim these factors at appropriate pathophysiologic targets. Although future therapeutic strategies in MS may be able to take advantage of these factors, such strategies will require an in-depth understanding of how these factors signal and how they are naturally targeted to axons and glia in both health and disease.
基于免疫调节疗法对多发性硬化症（MS）患者的疗效，传统上关于发病机制和治疗的许多研究与思考都集中在抑制免疫系统上。无论病因如何，最近的研究再次引发了这样一种观念，即MS患者的神经功能障碍与神经元（轴突）和神经胶质损伤程度最为相关。因此，作为理解MS发病机制和开发生物靶向新疗法的一种手段，需要更深入地了解轴突神经胶质生物学。轴突神经胶质生物学的核心是蛋白质调节因子，其中包括神经调节蛋白等神经生长因子以及在这些细胞类型之间传递信息且对神经系统发育至关重要的神经营养因子。遗憾的是，神经营养因子在治疗其他神经疾病方面的记录并不理想，部分原因是未能将这些因子靶向适当的病理生理靶点。尽管MS未来的治疗策略可能会利用这些因子，但此类策略将需要深入了解这些因子如何发出信号以及它们在健康和疾病状态下如何自然地靶向轴突和神经胶质。
