SLOW AXONAL TRANSPORT AND NEUROPATHY

缓慢的运输系统是增长、维护和 神经轴突的再生。基本功能包括装订 神经细丝和微管到移位机制和 许多胞质蛋白与这些细胞骨架的相干运输 元素。已经发表了一个理论模型，该模型是好的 与对慢波性质的许多观测结果定性一致 运输系统。该模型已被用来解释速度的提高。 某些神经毒物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，通过 哪一种方法可以估算吸附和吸附的原位反应常数 将运输的蛋白质解吸到运输装置 机制。有人建议利用这些理论发展来 分析文献中的数据和高质量的新数据 为此目的而准备的单个蛋白质的运输。 R.Lasek和P.Cancalon.从这些分析中获得的信息 应该为各种组件的交互提供新的见解 慢速交通系统之间的联系。通过整合这些内容 洞察和扩展模型，以包括当地的影响 沉积和退化，我们希望能够理解 确定放射性形状的机制 整个轴突的轮廓随时间变化。此外，还建议 扩展模型以包括多个神经丝-神经丝 相互作用，以使不断增长的神经丝状肿块的大小 估计是因为它们沿着轴突向下运输。这一分析应该 允许定量了解时间和位置的方式 运输受阻的发生是由于剂量计划和 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.