What is it about?
Tau is a protein that helps maintain the internal structure of nerve cells. It is produced in the cell body and transported along the axon, a long extension of the neuron, toward the axon terminal. Understanding how tau moves through neurons is important because abnormal tau is associated with neurological disorders such as Alzheimer’s disease. In this study, we developed a mathematical model that describes several ways tau can move: it can diffuse freely inside the axon, move along microtubules, or be carried by molecular motors. We then compared two possible outcomes when tau reaches the axon terminal. In one case, tau is removed there; in the other, it is not removed and its net flow at the terminal is zero.
Featured Image
Photo by Bioscience Image Library by Fayette Reynolds on Unsplash
Why is it important?
An important unresolved question is what happens to tau after it reaches the end of an axon. Our results show that simply measuring how much tau is present may not provide the answer. The total tau concentration differed by only about 15% between the two scenarios, and the percentage of tau bound to microtubules differed by only about 5%. In contrast, the predicted flow and average transport velocity of tau changed dramatically—by about two orders of magnitude—depending on what happened at the axon terminal. This suggests a practical way to distinguish between possible biological mechanisms: experimentally measuring the speed of tau transport and comparing it with model predictions may reveal what happens to tau when it reaches the terminal.
Perspectives
I find this work particularly interesting because it illustrates how mathematical modeling can help answer biological questions that are difficult to investigate directly. Instead of concentrating only on tau concentration, which might look quite similar under very different biological assumptions, the model identifies tau transport velocity and flux as potentially much more informative quantities. I also see this study as an example of how engineering and mathematical approaches can contribute to neuroscience. Tau transport is closely connected with diseases in which tau becomes abnormal and accumulates inside neurons. I hope that combining quantitative modeling with carefully designed experiments will ultimately help us better understand tau behavior in healthy and diseased nerve cells.
Andrey V Kuznetsov
North Carolina State University
Read the Original
This page is a summary of: Can numerical modeling help understand the fate of tau protein in the axon terminal?, Computer Methods in Biomechanics & Biomedical Engineering, January 2015, Taylor & Francis,
DOI: 10.1080/10255842.2014.994119.
You can read the full text:
Contributors
The following have contributed to this page
