Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
J Anat. 2014 Jan;224(1):36-44. doi: 10.1111/joa.12088. Epub 2013 Aug 13.
The pre-synaptic motor nerve terminal is a highly complex and dynamic compartment within the lower motor neuron responsible for converting electrical signals into secreted chemicals. This self-renewing process of synaptic transmission is accomplished by the calcium-triggered fusion of neurotransmitter-containing vesicles with the plasma membrane and the subsequent retrieval and recycling of vesicle components. Besides this conventional physiological role, the highly active process of vesicle fusion and re-uptake into endosomal sorting pathways acts as a conduit for entry of a range of substances into the intracellular compartment of the motor nerve terminal. Whilst this entry portal sub-serves many vital physiological processes, such as those mediated by neurotrophin trafficking, there is also the potential for substantial pathological consequences resulting from uptake of noxious agents, including autoantibodies, viruses and toxins. These may act locally to induce disease within the nerve terminal, or traffic beyond to the motor neuron cell body and central nervous system to exert their pathological effects. This review focuses on the recent evidence that the ganglioside-rich pre-synaptic membrane acts as a binding site for potentially neurotoxic serum autoantibodies that are present in human autoimmune motor neuropathies. Autoantibodies that bind surface antigens induce membrane lytic effects, whereas their uptake attenuates local injury and transfers any potential pathological consequences to the intracellular compartment. Herein the thesis is explored that a balance exists between local injury at the exofacial leaflet of the pre-synaptic membrane and antibody uptake, which dictates the overall level and site of motor nerve injury in this group of disorders.
突触前运动神经末梢是一个高度复杂和动态的区域，位于下运动神经元内，负责将电信号转化为分泌的化学物质。这种突触传递的自我更新过程是通过钙离子触发含有神经递质的囊泡与质膜融合来完成的，随后囊泡成分被回收和再循环。除了这种传统的生理作用外，囊泡融合和再摄取到内体分选途径的高度活跃过程充当了一系列物质进入运动神经末梢细胞内区室的入口。虽然这种进入门户服务于许多重要的生理过程，如神经生长因子的运输介导的过程，但也有可能由于摄入有害物质，包括自身抗体、病毒和毒素，导致实质性的病理后果。这些物质可能在神经末梢内局部引发疾病，或者通过运输到达运动神经元胞体和中枢神经系统，发挥其病理作用。本文综述了最近的证据，表明富含神经节苷脂的突触前膜作为人自身免疫性运动神经病中存在的潜在神经毒性血清自身抗体的结合位点。结合表面抗原的自身抗体诱导膜裂解效应，而其摄取则减轻局部损伤，并将任何潜在的病理后果转移到细胞内区室。本文探讨了这样一种观点，即在突触前膜外叶层的局部损伤和抗体摄取之间存在一种平衡，这种平衡决定了这组疾病中运动神经损伤的总体水平和部位。
