Shorrock Hannah K, Gillingwater Thomas H, Groen Ewout J N
Edinburgh Medical School: Biomedical Sciences, The University of Edinburgh, Edinburgh, United Kingdom.
Euan MacDonald Centre for Motor Neurone Disease Research, The University of Edinburgh, Edinburgh, United Kingdom.
Front Mol Neurosci. 2019 Mar 4;12:59. doi: 10.3389/fnmol.2019.00059. eCollection 2019.
Activation of skeletal muscle in response to acetylcholine release from the neuromuscular junction triggered by motor neuron firing forms the basis of all mammalian locomotion. Intricate feedback and control mechanisms, both from within the central nervous system and from sensory organs in the periphery, provide essential inputs that regulate and finetune motor neuron activity. Interestingly, in motor neuron diseases, such as spinal muscular atrophy (SMA), pathological studies in patients have identified alterations in multiple parts of the sensory-motor system. This has stimulated significant research efforts across a range of different animal models of SMA in order to understand these defects and their contribution to disease pathogenesis. Several recent studies have demonstrated that defects in sensory components of the sensory-motor system contribute to dysfunction of motor neurons early in the pathogenic process. In this review, we provide an overview of these findings, with a specific focus on studies that have provided mechanistic insights into the molecular processes that underlie dysfunction of the sensory-motor system in SMA. These findings highlight the role that cell types other than motor neurons play in SMA pathogenesis, and reinforce the need for therapeutic interventions that target and rescue the wide array of defects that occur in SMA.
运动神经元放电触发神经肌肉接头处乙酰胆碱释放，从而激活骨骼肌，这构成了所有哺乳动物运动的基础。来自中枢神经系统内部和外周感觉器官的复杂反馈和控制机制提供了调节和微调运动神经元活动的重要输入。有趣的是，在运动神经元疾病中，如脊髓性肌萎缩症（SMA），对患者的病理研究已确定感觉运动系统多个部位存在改变。这激发了对一系列不同SMA动物模型的大量研究工作，以了解这些缺陷及其对疾病发病机制的影响。最近的几项研究表明，感觉运动系统感觉成分的缺陷在致病过程早期导致运动神经元功能障碍。在这篇综述中，我们概述了这些发现，特别关注那些对SMA感觉运动系统功能障碍背后的分子过程提供了机制性见解的研究。这些发现突出了运动神经元以外的细胞类型在SMA发病机制中的作用，并强化了针对并挽救SMA中出现的各种缺陷的治疗干预措施的必要性。
