Mechanisms and treatment strategies of demyelinating and dysmyelinating Charcot-Marie-Tooth disease  

作　　者：Nadège Hertzog Claire Jacob 

机构地区：[1]Faculty of Biology,Institute of Developmental Biology and Neurobiology,Johannes Gutenberg University Mainz,Hanns-Dieter-Hüsch-Weg,Mainz,Germany

出　　处：《Neural Regeneration Research》2023年第9期1931-1939,共9页中国神经再生研究（英文版）

基　　金：supported by the Deutsche Forschungsgemeinshaft (to CJ)。

摘　　要：Schwann cells,the myelinating glia of the peripheral nervous system,wrap axons multiple times to build their myelin sheath.Myelin is of paramount importance for axonal integrity and fast axon potential propagation.However,myelin is lacking or dysfunctional in several neuropathies including demyelinating and dysmyelinating Charcot-M arie-To oth disease.Charcot-Marie-To oth disease represents the most prevalent inherited neuropathy in humans and is classified either as axonal,demyelinating or dysmyelinating,or as intermediate.The demyelinating or dysmyelinating forms of Charcot-Marie-Tooth disease constitute the majority of the disease cases and are most frequently due to mutations in the three following myelin genes:peripheral myelin protein 22,myelin protein ze ro and gap junction beta 1(coding for Connexin 32) causing Charcot-M arie-Tooth disease type 1A,Charcot-Marie-Tooth disease type 1B,and X-linked Charcot-M arie-Tooth disease type 1,respectively.The resulting perturbation of myelin structure and function leads to axonal demyelination or dysmyelination and causes severe disabilities in affected patients.No treatment to cure or slow down the disease progression is currently available on the market,howeve r,scientific discoveries led to a better understanding of the pathomechanisms of the disease and to potential treatment strategies.In this review,we describe the features and molecular mechanisms of the three main demyelinating or dysmyelinating forms of Charcot-Marie-Tooth disease,the rodent models used in research,and the emerging therapeutic approaches to cure or counteract the progression of the disease.

关 键 词：Charcot-Marie-Tooth disease rodent models emerging treatments demyelination and dysmyelination endoplasmic reticulum stress gene therapy MYELIN repair Schwann cells unfolded protein response 

分 类 号：R744.5[医药卫生—神经病学与精神病学]