Department of Neurosciences, Center for Translational Neurosciences, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA.
Dis Model Mech. 2010 Sep-Oct;3(9-10):535-9. doi: 10.1242/dmm.001958. Epub 2010 Jul 20.
Multiple sclerosis (MS) is considered an autoimmune-mediated demyelinating disease that targets the central nervous system (CNS). Despite considerable research efforts over multiple decades, our understanding of the basic biological processes that are targeted in the disease and the mechanisms of pathogenesis are poorly understood. Consequently, current therapies directed at controlling the progression of the disease are limited in their effectiveness. Historically, the primary focus of MS research has been to define the cellular and molecular basis of the immunological pathogenic mechanisms. Recently, however, it has become clear that long-term functional recovery in MS will require the development of strategies that facilitate myelin repair in lesion areas. The emerging evidence that the adult vertebrate CNS retains the capacity to regenerate neural cells that have been lost to disease or damage has provoked intensive research focused on defining the mechanisms of myelin repair. Unfortunately, the existing animal models of MS are poorly equipped to assess myelin repair, and new validated strategies to identify therapeutics targeted at promoting myelin repair are badly needed. This Commentary will review established murine models of MS, and discuss emerging technologies that promise to provide insights into the mechanisms of myelin repair.
多发性硬化症(MS)被认为是一种自身免疫介导的脱髓鞘疾病,其靶器官为中枢神经系统(CNS)。尽管经过了数十年的大量研究,但我们对疾病中靶向的基本生物学过程和发病机制的了解仍很有限。因此,目前针对控制疾病进展的治疗方法效果有限。从历史上看,MS 研究的主要重点是确定免疫发病机制的细胞和分子基础。然而,最近已经很清楚,MS 的长期功能恢复将需要制定策略来促进病变区域髓鞘修复。有新的证据表明,成年脊椎动物中枢神经系统保留了再生因疾病或损伤而丧失的神经细胞的能力,这激发了针对定义髓鞘修复机制的密集研究。不幸的是,现有的 MS 动物模型在评估髓鞘修复方面能力不足,迫切需要新的经过验证的策略来确定针对促进髓鞘修复的治疗方法。本文述评将回顾已建立的 MS 啮齿动物模型,并讨论新兴技术,这些技术有望深入了解髓鞘修复的机制。