Department of Research, Sir Ganga Ram Hospital, Delhi, India.
Department of Biotechnology, Jamia Hamdard, Delhi, India.
Mol Neurobiol. 2022 Mar;59(3):1502-1527. doi: 10.1007/s12035-021-02658-6. Epub 2022 Jan 8.
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by progressive degeneration of motor neurons leading to skeletal muscle denervation. Earlier studies have shown that motor neuron degeneration begins in motor cortex and descends to the neuromuscular junction (NMJ) in a dying forward fashion. However, accumulating evidences support that ALS is a distal axonopathy where early pathological changes occur at the NMJ, prior to onset of clinical symptoms and propagates towards the motor neuron cell body supporting "dying back" hypothesis. Despite several evidences, series of events triggering NMJ disassembly in ALS are still obscure. Neuromuscular junction is a specialized tripartite chemical synapse which involves a well-coordinated communication among the presynaptic motor neuron, postsynaptic skeletal muscle, and terminal Schwann cells. This review provides comprehensive insight into the role of NMJ in ALS pathogenesis. We have emphasized the molecular alterations in cellular components of NMJ leading to loss of effective neuromuscular transmission in ALS. Further, we provide a preview into research involved in exploring NMJ as potential target for designing effective therapies for ALS.
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，其特征是运动神经元进行性退化，导致骨骼肌去神经支配。早期研究表明，运动神经元退化始于运动皮层，并以死亡前的方式下降到运动终板（NMJ）。然而，越来越多的证据支持 ALS 是一种远端轴索性疾病，在临床症状出现之前，NMJ 就已经发生了早期的病理变化，并向运动神经元胞体传播，支持“退行性”假说。尽管有几项证据表明，触发 NMJ 解体的一系列事件在 ALS 中仍然不清楚。运动终板是一种特殊的三部分化学突触，涉及到突触前运动神经元、突触后骨骼肌和终末施万细胞之间的协调通信。这篇综述全面深入地探讨了 NMJ 在 ALS 发病机制中的作用。我们强调了 NMJ 细胞成分的分子改变导致 ALS 中有效的神经肌肉传递丧失。此外，我们还预览了 NMJ 作为设计治疗 ALS 有效疗法的潜在靶点的研究。
