脊髓延髓肌萎缩症（肯尼迪病）的分子发病机制与治疗途径。
Molecular pathogenesis of spinal bulbar muscular atrophy (Kennedy's disease) and avenues for treatment.
机构信息
National Institutes of Health, Bethesda, Maryland, USA.
出版信息
Curr Opin Neurol. 2020 Oct;33(5):629-634. doi: 10.1097/WCO.0000000000000856.
Abstract
PURPOSE OF REVIEW
The aim of this study was to illustrate the current understanding and avenues for developing treatment in spinal and bulbar muscular atrophy (SBMA), an inherited neuromuscular disorder caused by a CAG trinucleotide repeat expansion in the androgen receptor (AR) gene.
RECENT FINDINGS
Important advances have been made in characterizing the molecular mechanism of the disease, including the disruption of protein homeostasis, intracellular trafficking and signalling pathways. Biomarkers such as MRI quantification of muscle volume and fat fraction have been used to track disease progression, and will be useful in future clinical studies. Therapies tested and under development have been based on diverse strategies, including targeting mutant AR gene expression, stability and activity, and pathways that mitigate disease toxicity.
SUMMARY
We provide an overview of the recent advances in understanding the SBMA disease mechanism and highlight efforts to translate these insights into well tolerated and effective therapy.
摘要
目的综述
本研究旨在阐述目前对脊髓和延髓肌萎缩症 (SBMA) 的治疗理解和研究途径，SBMA 是一种遗传性神经肌肉疾病，由雄激素受体 (AR) 基因中的 CAG 三核苷酸重复扩展引起。
最新发现
在阐明疾病的分子机制方面取得了重要进展，包括对蛋白质稳态、细胞内运输和信号通路的破坏。磁共振成像 (MRI) 定量测量肌肉体积和脂肪分数等生物标志物已被用于跟踪疾病进展，并将在未来的临床研究中发挥重要作用。已测试和正在开发的治疗方法基于多种策略，包括靶向突变 AR 基因表达、稳定性和活性，以及减轻疾病毒性的途径。
总结
我们概述了对 SBMA 疾病机制的最新理解，并强调了将这些见解转化为耐受良好且有效的治疗方法的努力。
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