SLOW AXONAL TRANSPORT AND NEUROPATHY

缓慢的运输系统是基本的增长，维护， 神经轴突的再生 基本特征包括绑定 神经丝和微管的易位机制， 许多胞质蛋白质与这些细胞骨架的连贯运输 元素 已经发表了一个理论模型， 定性协议与许多意见的性质缓慢 运输系统。 该模型已被用来解释加速的 某些神经毒素诱导的神经丝转运率 神经病 进一步的理论研究提供了一种技术， 可以估计吸附的原位大鼠常数， 将转运蛋白解吸至转运体 机制 建议利用这些理论发展， 分析文献中的数据和高质量的新数据， 个别蛋白质的运输正在为此目的准备博士。 R. Lasek和P. Cancalon。 从这些分析中获得的信息 应该提供新的洞察力的相互作用的各种组成部分， 缓慢的交通系统的一部分 通过将这些 洞察力和扩展模型，包括当地的影响， 沉积和降解，我们希望能够了解 决定放射性形状的机制 在轴突上的分布图。 还拟议 扩展模型以包括多个神经元-神经丝 相互作用，以便生长的神经丝状物质的大小可以 估计它们是沿着轴突运输的。 这种分析应当 可以定量地了解时间和位置 转运的阻断是剂量方案的函数， 神经毒剂的反应性。

The slow transport system is fundamental to the growth, maintenance, and regeneration of nerve axons. The essential features include the binding of neurofilaments and microtubules to a translocating mechanism and the coherent transport of many cytosolic proteins with these cytoskeletal elements. A theoretical model has been published which is in good qualitative agreement with many observations of properties of the slow transport system. The model has been used to explain the speed up of neurofilament transport rates in certain neurotoxicant-induced neuropathies. Further theoretical studies have provided a technique by which one could estimate the in-situ rat constants for the adsorption and desorption of the transported proteins to the transport mechanism. It is proposed to use these theoretical developments to analyze both data in the literature and new data of high quality on the transport of individual proteins being prepared for this purpose by Drs. R. Lasek and P. Cancalon. The information gained from these analyses should provide new insight into the interaction of the various components of the slow transport system with one another. By incorporating these insights and extending the model to include the effects of local deposition and degradation, we expect to be able to understand the mechanisms responsible for determining the shape of the radioactivity profile throughout the axon as a function of time. It is also proposed to extend the model to include multiple neurofilament-neurofilament interactions so that the size of growing neurofilamentous masses can be estimated as they are transported down the axon. This analysis should allow quantitative understanding of the way in which the time and position of the blockage of transport occurs as a function of dose schedule and reactivity of the neurotoxicant.