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SLOW AXONAL TRANSPORT AND NEUROPATHY

轴突运输缓慢与神经病变

基本信息

批准号：
3410402
负责人：
MICHAEL REED
金额：
$ 12.92万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-01-01 至 1993-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3410402
关键词：
axon biological transport cell cell interaction computer simulation mathematical model nervous system disorder neurofilament neurogenesis neuronal transport neurotoxins protein transport radiotracer

项目摘要

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.

缓慢的运输系统对于增长、维护和发展至关重要神经轴突的再生。基本功能包括绑定神经丝和微管的易位机制和许多胞浆蛋白与这些细胞骨架的相干运输元素。已发表理论模型，效果良好与慢速特性的许多观察结果定性一致运输系统。该模型被用来解释加速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可以估计吸附的原位大鼠常数和将运输的蛋白质解吸至运输机制。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博士们为此目的准备了单个蛋白质的运输。 R. Lasek 和 P. Cancalon。从这些分析中获得的信息应该为各个组件的交互提供新的见解彼此之间的慢速运输系统。通过合并这些见解并扩展模型以包括当地的影响沉积和降解，我们希望能够理解负责确定放射性形状的机制整个轴突的轮廓作为时间的函数。还建议扩展模型以包括多个神经丝-神经丝相互作用，以便生长的神经丝状团块的大小可以当它们沿着轴突运输时估计。这个分析应该允许定量地理解时间和位置的方式运输阻塞的发生是剂量计划的函数，并且神经毒剂的反应性。