Nave Klaus-Armin, Sereda Michael W, Ehrenreich Hannelore
Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
Nat Clin Pract Neurol. 2007 Aug;3(8):453-64. doi: 10.1038/ncpneuro0583.
The hereditary motor and sensory neuropathies (also known as Charcot-Marie-Tooth disease or CMT) are characterized by a length-dependent loss of axonal integrity in the PNS, which leads to progressive muscle weakness and sensory deficits. The 'demyelinating' neuropathies (CMT disease types 1 and 4) are genetically heterogeneous, but their common feature is that the primary defect perturbs myelination. As we discuss in this Review, several new genes associated with CMT1 and CMT4 have recently been identified. The emerging view is that a range of different subcellular defects in Schwann cells can cause axonal loss, which represents the final common pathway of all CMT disease and is independent of demyelination. We propose that Schwann cells provide a first line of axonal neuroprotection. A better understanding of axon-glia interactions should open the way to therapeutic interventions for demyelinating neuropathies. Transgenic animal models have become essential for dissecting CMT disease mechanisms and exploring novel therapies.
遗传性运动和感觉神经病（也称为夏科-马里-图斯病或CMT）的特征是外周神经系统（PNS）中轴突完整性出现长度依赖性丧失，这会导致进行性肌肉无力和感觉缺陷。“脱髓鞘”性神经病（CMT病1型和4型）在遗传上具有异质性，但其共同特征是主要缺陷扰乱了髓鞘形成。正如我们在本综述中所讨论的，最近已鉴定出几种与CMT1和CMT4相关的新基因。新出现的观点是，施万细胞中一系列不同的亚细胞缺陷可导致轴突丧失，这是所有CMT疾病的最终共同途径，且与脱髓鞘无关。我们提出施万细胞提供了轴突神经保护的第一道防线。更好地理解轴突-神经胶质细胞相互作用应该为脱髓鞘性神经病的治疗干预开辟道路。转基因动物模型对于剖析CMT疾病机制和探索新疗法已变得至关重要。
