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Pathogenesis and Treatment Strategies of Motor Neuron Diseases as Functions of Retrograde Axoplasmic Transport

逆行轴浆运输功能的运动神经元疾病的发病机制和治疗策略

基本信息

批准号：
60480219
负责人：
YAMAMOTO Teiji
金额：
$ 3.26万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1987
项目状态：
已结题

项目摘要

In order to determine the roles of axoplasmic transport in pathogenesis of motor neuron diseases, following studies have been carried out during 1985-1987 period.1. Role of retrograde axoplasmic transport for survival and death of motor neurons: Although somatic motor neurons are protected by the blood-brain barrier (BBB), their axons and endings distributed widely onto the neuromuscular junctions are exempted from BBB. When Adriamycin, a RNA inhibitor, or ricinus communis agglutinin, an inhibitor of protein synthesis, was injected into the rat sciatic nerve, these substanoes were inoorporated into their soma and within several days to weeks somatic motor neurons contributing to the sciatic nerve underwent selective degeneration. This is thought to be a form of experimental motor neuron disease. The role of retrograde axoplasmic transport for survival of motor neurons is evident from these studies.2. Retrograde axoplasmic transport of serum proteins into somatic motor neurons: By immun … More ocytochemistry, motor neurons were found normally to inoorporate serum albumin and immunoglobulin G into their cell body by axoplasmic flow from the neuromuscular junction. Albumin binds to diverse substanoes; e.g. a variety of drugs and several metal ions.It is possible therefore that motor neurons might integrate through retrograde axoplasmic flow some neurotoxic substanoes which do not permeate the BBB. Chronic egress of some unknown neurotoxic substanoes via this route might endanger the survival of somatic motor neurons.3. Retrograde axoplasmic transport of neuromuscular junctional extracellular matrix proteins: Laminin, a component of basement membrane and known to exert a potent neurotrophic activity in vitro, was for the first time demonstrated immunocytochemically in motor neurons. This large glyooprotein, or its fragmant might be an important messenger for motor neurons.These studies have clearly shown the important roles of retrograde axoplasmic transport in maintenanoe and survival of motor neurons. Conversely, as a future treatment strategy, drug delivery selectively to motor neurons may be achieved circumventing the BBB when the retrograde axoplasmic transport is utilized. Less

为了确定轴浆转运在运动神经元病发病机制中的作用，在1985-1987年间进行了以下研究。逆行轴浆运输在运动神经元存活和死亡中的作用：尽管躯体运动神经元受到血脑屏障(BBB)的保护，但它们广泛分布在神经肌肉接头上的轴突和终末不受血脑屏障的保护。将RNA抑制剂阿霉素或蛋白质合成抑制剂蓖麻凝集素注入大鼠坐骨神经，这些物质被注入其胞体，在几天到几周内，对坐骨神经有贡献的躯体运动神经元发生选择性变性。这被认为是实验性运动神经元疾病的一种形式。从这些研究中可以明显看出逆行轴浆运输对于运动神经元存活的作用。免疫…法研究血清蛋白逆行轴浆转运至躯体运动神经元更多的细胞化学和运动神经元通过轴浆流从神经肌肉连接处正常地将血清白蛋白和免疫球蛋白G送入细胞体。白蛋白与多种物质结合，如多种药物和几种金属离子。因此，运动神经元可能通过逆行轴浆流动整合一些不渗透到血脑屏障的神经毒性物质。一些未知的神经毒性物质通过这一途径慢性排出，可能危及躯体运动神经元的存活。神经肌肉连接细胞外基质蛋白的逆行轴浆运输：层粘连蛋白是基底膜的一种成分，在体外具有强大的神经营养活性，首次在运动神经元中被证明是免疫细胞化学的结果。这种大的糖蛋白或其碎片可能是运动神经元的重要信使。这些研究清楚地表明了逆行轴浆运输在维持运动神经元和存活中的重要作用。相反，作为一种未来的治疗策略，当利用逆行轴浆运输时，可以绕过血脑屏障选择性地将药物输送到运动神经元。较少