Center for Gene Therapy, The Abigail Wexner Research Institute at Nationwide Children's Hospital, 575 Children's Crossroad, Columbus, OH 43215, USA.
Molecular, Cellular, and Developmental Biology Program, The Ohio State University, Columbus, OH 43210, USA.
Int J Mol Sci. 2024 Aug 26;25(17):9227. doi: 10.3390/ijms25179227.
Charcot-Marie-Tooth type 1B (CMT1B) is a peripheral neuropathy caused by mutations in the gene encoding myelin protein zero (MPZ), a key component of the myelin sheath in Schwann cells. Mutations in the gene can lead to protein misfolding, unfolded protein response (UPR), endoplasmic reticulum (ER) stress, or protein mistrafficking. Despite significant progress in understanding the disease mechanisms, there is currently no effective treatment for CMT1B, with therapeutic strategies primarily focused on supportive care. Gene therapy represents a promising therapeutic approach for treating CMT1B. To develop a treatment and better design preclinical studies, an in-depth understanding of the pathophysiological mechanisms and animal models is essential. In this review, we present a comprehensive overview of the disease mechanisms, preclinical models, and recent advancements in therapeutic research for CMT1B, while also addressing the existing challenges in the field. This review aims to deepen the understanding of CMT1B and to encourage further research towards the development of effective treatments for CMT1B patients.
CMT1B 是一种周围神经病，由编码髓鞘蛋白零（MPZ）的基因突变引起，MPZ 是施旺细胞髓鞘的关键成分。基因中的突变可导致蛋白质错误折叠、未折叠蛋白反应（UPR）、内质网（ER）应激或蛋白质运输错误。尽管在了解疾病机制方面取得了重大进展，但目前尚无有效的 CMT1B 治疗方法，治疗策略主要集中在支持性护理上。基因治疗是治疗 CMT1B 的一种很有前途的治疗方法。为了开发治疗方法并更好地设计临床前研究，深入了解病理生理机制和动物模型至关重要。在这篇综述中，我们全面介绍了 CMT1B 的疾病机制、临床前模型和治疗研究的最新进展，同时也解决了该领域的现有挑战。本综述旨在加深对 CMT1B 的理解，并鼓励进一步研究，为 CMT1B 患者开发有效的治疗方法。
