轴突起始段tau蛋白转运的模型化
Modeling tau transport in the axon initial segment
摘要：
通过假设tau蛋白可以处于七种动力学状态，我们建立了tau蛋白在轴突和轴突起始段（AIS）中转运的模型。两组单独的动力学常数进行了测定，一个在轴突和其他的AIS。这是通过将轴突中的模型预测与实验结果拟合以及通过将AIS中的模型预测与AIS中总tau浓度的假定线性增加拟合来完成的。校准模型用于预测轴突和AIS中的tau转运。据我们所知，这是第一篇论文，提出了一个数学模型的tau运输的AIS。我们的建模结果表明，游离tau与MT的结合在AIS中产生了游离tau的负梯度。这导致扩散驱动的tau从胞体转运到AIS中。该模型进一步表明，tau的缓慢轴突运输和扩散驱动的运输在AIS中一起工作，使tau顺行移动。我们的数值结果预测这两种机制之间的相互作用：随着距离的增加，从胞体，扩散驱动的运输减少，而电机驱动的运输变得更大。因此，AIS中的机器就像一个泵，将tau蛋白转移到轴突中。
英文摘要：
By assuming that tau protein can be in seven kinetic states, we developed a model of tau protein transport in the axon and in the axon initial segment (AIS). Two separate sets of kinetic constants were determined, one in the axon and the other in the AIS. This was done by fitting the model predictions in the axon with experimental results and by fitting the model predictions in the AIS with the assumed linear increase of the total tau concentration in the AIS. The calibrated model was used to make predictions about tau transport in the axon and in the AIS. To the best of our knowledge, this is the first paper that presents a mathematical model of tau transport in the AIS. Our modeling results suggest that binding of free tau to MTs creates a negative gradient of free tau in the AIS. This leads to diffusion-driven tau transport from the soma into the AIS. The model further suggests that slow axonal transport and diffusion-driven transport of tau work together in the AIS, moving tau anterogradely. Our numerical results predict an interplay between these two mechanisms: as the distance from the soma increases, the diffusion-driven transport decreases, while motor-driven transport becomes larger. Thus, the machinery in the AIS works as a pump, moving tau into the axon.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
