Markworth Ronja, Bähr Mathias, Burk Katja
Department of Neurology, University Medical Center Göttingen, Göttingen, Germany.
Center for Biostructural Imaging of Neurodegeneration, Göttingen, Germany.
Front Mol Neurosci. 2021 Aug 16;14:695294. doi: 10.3389/fnmol.2021.695294. eCollection 2021.
Charcot-Marie-Tooth disease (CMT), also known as motor and sensory neuropathy, describes a clinically and genetically heterogenous group of disorders affecting the peripheral nervous system. CMT typically arises in early adulthood and is manifested by progressive loss of motor and sensory functions; however, the mechanisms leading to the pathogenesis are not fully understood. In this review, we discuss disrupted intracellular transport as a common denominator in the pathogenesis of different CMT subtypes. Intracellular transport via the endosomal system is essential for the delivery of lipids, proteins, and organelles bidirectionally to synapses and the soma. As neurons of the peripheral nervous system are amongst the longest neurons in the human body, they are particularly susceptible to damage of the intracellular transport system, leading to a loss in axonal integrity and neuronal death. Interestingly, defects in intracellular transport, both in neurons and Schwann cells, have been found to provoke disease. This review explains the mechanisms of trafficking and subsequently summarizes and discusses the latest findings on how defects in trafficking lead to CMT. A deeper understanding of intracellular trafficking defects in CMT will expand our understanding of CMT pathogenesis and will provide novel approaches for therapeutic treatments.
夏科-马里-图斯病（CMT），也称为运动和感觉神经病变，是一组临床和遗传异质性疾病，影响周围神经系统。CMT通常在成年早期发病，表现为运动和感觉功能的进行性丧失；然而，导致发病机制的原因尚未完全了解。在这篇综述中，我们讨论细胞内运输紊乱是不同CMT亚型发病机制的一个共同因素。通过内体系统的细胞内运输对于脂质、蛋白质和细胞器双向运输到突触和胞体至关重要。由于周围神经系统的神经元是人体中最长的神经元之一，它们特别容易受到细胞内运输系统损伤的影响，导致轴突完整性丧失和神经元死亡。有趣的是，已经发现神经元和施万细胞中的细胞内运输缺陷都会引发疾病。这篇综述解释了运输机制，随后总结并讨论了关于运输缺陷如何导致CMT的最新发现。对CMT中细胞内运输缺陷的更深入理解将扩展我们对CMT发病机制的认识，并将为治疗提供新的方法。
