Remyelination in multiple sclerosis.
Remyelination in multiple sclerosis.
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DOI：
10.1016/s0074-7742(07)79026-8
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发表时间：
2007
影响因子：
--
通讯作者：
Chari DM
中科院分区：
文献类型：
--
作者：
Chari DM
再髓鞘形成是指在成年中枢神经系统（CNS）的轴突周围产生新的髓鞘的现象。这是在多发性硬化症（MS）等疾病中髓鞘的病理性丢失之后。再髓鞘化可以恢复轴突的传导特性（从而恢复神经功能），并且越来越多地被认为对轴突发挥神经保护作用。在许多MS病变中发生再髓鞘化，但在大多数病变和患者中变得越来越不完全/不充分，最终失败。努力了解这种再生失败的原因，推动了对髓鞘再生生物学以及调节这一过程的复杂，相互依赖的细胞和分子因子的研究。对实验性损伤修复机制的研究表明，髓鞘再生发生在两个主要阶段。第一个由少突胶质细胞祖细胞（OPCs）的病变定殖组成，第二个是OPCs分化成髓鞘形成的少突胶质细胞，其接触脱髓鞘轴突以产生功能性髓鞘。已经鉴定了介导这两个修复阶段的几种细胞内和细胞外分子。从理论上讲，脱髓鞘病变的修复可以通过增强内在修复过程（通过提供一种或多种髓鞘再生增强因子或通过免疫球蛋白治疗）来促进。或者，内源性修复可以通过将髓鞘生成细胞引入脱髓鞘区域来绕过;已经鉴定了几种细胞候选物，其可以介导实验性脱髓鞘病变的修复。促进髓鞘再生的治疗策略所面临的未来挑战将涉及将基础科学的发现转化为临床脱髓鞘疾病。
Remyelination is the phenomenon by which new myelin sheaths are generated around axons in the adult central nervous system (CNS). This follows the pathological loss of myelin in diseases like multiple sclerosis (MS). Remyelination can restore conduction properties to axons (thereby restoring neurological function) and is increasingly believed to exert a neuroprotective role on axons. Remyelination occurs in many MS lesions but becomes increasingly incomplete/inadequate and eventually fails in the majority of lesions and patients. Efforts to understand the causes for this failure of regeneration have fueled research into the biology of remyelination and the complex, interdependent cellular and molecular factors that regulate this process. Examination of the mechanisms of repair of experimental lesions has demonstrated that remyelination occurs in two major phases. The first consists of colonization of lesions by oligodendrocyte progenitor cells (OPCs), the second the differentiation of OPCs into myelinating oligodendrocytes that contact demyelinated axons to generate functional myelin sheaths. Several intracellular and extracellular molecules have been identified that mediate these two phases of repair. Theoretically, the repair of demyelinating lesions can be promoted by enhancing the intrinsic repair process (by providing one or more remyelination‐enhancing factors or via immunoglobulin therapy). Alternatively, endogenous repair can be bypassed by introducing myelinogenic cells into demyelinated areas; several cellular candidates have been identified that can mediate repair of experimental demyelinating lesions. Future challenges confronting therapeutic strategies to enhance remyelination will involve the translation of findings from basic science to clinical demyelinating disease.