和谐失调：运动神经元病中神经肌肉接头的细胞间通讯。

Harmony Lost: Cell-Cell Communication at the Neuromuscular Junction in Motor Neuron Disease.

机构信息

Biomedical Sciences Graduate Program, University of California San Diego, La Jolla, CA 92093, USA; Department of Pathology and Laboratory Medicine and Department of Neurology, University of California Irvine, Irvine, CA 92697, USA.

Department of Pathology and Laboratory Medicine and Department of Neurology, University of California Irvine, Irvine, CA 92697, USA; Department of Neurology, Duke University School of Medicine, Durham, NC 27710, USA.

出版信息

Trends Neurosci. 2020 Sep;43(9):709-724. doi: 10.1016/j.tins.2020.07.002.

DOI:10.1016/j.tins.2020.07.002

PMID:32846148

Abstract

The neuromuscular junction (NMJ) is a specialized synapse that is the point of connection between motor neurons and skeletal muscle. Although developmental studies have established the importance of cell-cell communication at the NMJ for the integrity and full functionality of this synapse, the contribution of this structure as a primary driver in motor neuron disease pathogenesis remains uncertain. Here, we consider the biology of the NMJ and review emerging lines of investigation that are highlighting the importance of cell-cell interaction at the NMJ in spinal muscular atrophy (SMA), X-linked spinal and bulbar muscular atrophy (SBMA), and amyotrophic lateral sclerosis (ALS). Ongoing research may reveal NMJ targets and pathways whose therapeutic modulation will help slow the progression of motor neuron disease, offering a novel treatment paradigm for ALS, SBMA, SMA, and related disorders.

摘要

神经肌肉接头（NMJ）是一种特化的突触，是运动神经元和骨骼肌之间的连接点。尽管发育研究已经确定了 NMJ 处细胞间通讯对于该突触的完整性和全功能的重要性，但该结构作为运动神经元疾病发病机制的主要驱动因素的贡献仍然不确定。在这里，我们考虑 NMJ 的生物学，并回顾新兴的研究路线，这些研究路线强调了 NMJ 处细胞间相互作用在脊髓性肌萎缩症（SMA）、X 连锁脊髓和延髓肌肉萎缩症（SBMA）和肌萎缩侧索硬化症（ALS）中的重要性。正在进行的研究可能会揭示 NMJ 靶点和途径，其治疗调节将有助于减缓运动神经元疾病的进展，为 ALS、SBMA、SMA 和相关疾病提供新的治疗范例。