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Studies of specific treatment strategies utilizing axoplasmic transpot in motor neuron diseases.

利用轴浆转运治疗运动神经元疾病的具体治疗策略的研究。

基本信息

批准号：
63480214
负责人：
YAMAMOTO Teiji
金额：
$ 3.9万
依托单位：
Fukushima Medical College (1989)Tohoku University (1988)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

项目摘要

In order to investigate the possibility of treating the patients with amyotrophic lateral sclerosis, utilizing the phenomenon of retrograde axoplasmic transport, intrinsic transport mechanism was initially studied. This study clarified the somatic motor neurons residing in the spinal anterior horn physiologically take up serum albumin and IgG by way of retrograde axoplasmic transport from the neuromuscular junction. Extracellular matrix forming the neuromuscular junction was then thought to play a role in subserving the reservoir for initial uptake, constituent proteins of the extracellular matrix were examined. Laminin, one of major proteins of the matrix, is known to possess many functional domains, one of which is a potent neurotrophic actions. When motor neurons were immunocytochemically studies with anti-laminin antibody, there was a distinct immunoreactivity in motor neurons. Western blot of the brain homogenates in rat and human disclosed l9OkDalton protein which shares the antigenicity with authentic laminin was found. When the laminin in the CNS (neurolaminin) was compared to authentic laminin, it was found that neurolaminin did not possess subunits under reducing condition and the molecular weight is close to laminin B chain. However, heparin-binding domain appeared not present in neurolaminin, when heparin-affinity column was used. Similarly, neurolaminin did not appear to be an extracellular metric constituent but intra cellular molecule. The study is in progress in order to purify neurolaminin and to see the biological activities which are assumed to be present in this particular molecule. If indeed neurolaminin possesses neurotrophic activity this molecule might be the one which is worthwhile trying to treat the patients with amyotrophic lateral sclerosis, by way of retrograde axoplasmic transport system.

为了探讨肌萎缩侧索硬化症治疗的可能性，利用逆行轴浆转运现象，对内源性转运机制进行了初步研究。本研究阐明了脊髓前角躯体运动神经元对血清白蛋白和IgG的摄取是通过神经肌肉接头的逆行轴浆转运实现的。细胞外基质形成的神经肌肉接头，然后被认为发挥作用，在subserving水库的初始摄取，细胞外基质的组成蛋白进行了检查。层粘连蛋白是基质的主要蛋白质之一，具有多种功能结构域，其中之一是具有强的神经营养作用。当用抗层粘连蛋白抗体对运动神经元进行免疫细胞化学研究时，运动神经元中存在明显的免疫反应性。Western blot结果显示，在大鼠和人脑匀浆中发现了与真实层粘连蛋白具有相同抗原性的190kD蛋白，与真实层粘连蛋白比较，发现神经层粘连蛋白在还原条件下不具有亚基，分子量接近于层粘连蛋白B链。然而，肝素结合域似乎不存在于神经层粘连蛋白，当肝素亲和柱。类似地，神经层粘连蛋白似乎不是细胞外计量成分，而是细胞内分子。这项研究正在进行中，以纯化神经层粘连蛋白，并观察假定存在于这种特定分子中的生物活性。如果神经层粘连蛋白确实具有神经营养活性，那么这种分子可能是值得尝试通过逆行轴浆运输系统治疗肌萎缩侧索硬化症患者的分子。