Barrow Neurological Institute, Phoenix, AZ, USA.
College of Medicine, University of Arizona, Phoenix, AZ, USA.
Brain. 2023 Nov 2;146(11):4425-4436. doi: 10.1093/brain/awad202.
Amyotrophic lateral sclerosis (ALS), the major adult-onset motor neuron disease, has been viewed almost exclusively as a disease of upper and lower motor neurons, with muscle changes interpreted as a consequence of the progressive loss of motor neurons and neuromuscular junctions. This has led to the prevailing view that the involvement of muscle in ALS is only secondary to motor neuron loss. Skeletal muscle and motor neurons reciprocally influence their respective development and constitute a single functional unit. In ALS, multiple studies indicate that skeletal muscle dysfunction might contribute to progressive muscle weakness, as well as to the final demise of neuromuscular junctions and motor neurons. Furthermore, skeletal muscle has been shown to participate in disease pathogenesis of several monogenic diseases closely related to ALS. Here, we move the narrative towards a better appreciation of muscle as a contributor of disease in ALS. We review the various potential roles of skeletal muscle cells in ALS, from passive bystanders to active players in ALS pathophysiology. We also compare ALS to other motor neuron diseases and draw perspectives for future research and treatment.
肌萎缩侧索硬化症（ALS）是一种主要的成年起病的运动神经元疾病，几乎完全被视为上运动神经元和下运动神经元疾病，肌肉变化被解释为运动神经元和神经肌肉接头进行性丧失的结果。这导致了目前的观点，即肌肉在 ALS 中的参与仅仅是运动神经元丧失的继发结果。骨骼肌和运动神经元相互影响各自的发育，并构成一个单一的功能单元。在 ALS 中，多项研究表明，骨骼肌功能障碍可能导致进行性肌肉无力，以及神经肌肉接头和运动神经元的最终死亡。此外，已经表明骨骼肌参与了与 ALS 密切相关的几种单基因疾病的发病机制。在这里，我们将叙述方式转向更好地理解肌肉在 ALS 中的作用。我们回顾了骨骼肌细胞在 ALS 中的各种潜在作用，从被动旁观者到 ALS 病理生理学中的主动参与者。我们还将 ALS 与其他运动神经元疾病进行了比较，并为未来的研究和治疗提供了观点。
