MITF in the Regulation of Schwann Cell Nerve Repair Activity – Fight Aging!

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The peripheral nervous system is far more capable of self-repair than the central nervous system. Nonetheless, nerve damage typically results in far less functional regeneration than is the case for other tissues. The research community is thus interested in finding ways to enhance existing repair processes. Here, researchers investigate a portion of the regulatory mechanisms that control the activity of Schwann cells in nerve repair, in search of targets for drug development programs aimed at enhancing regeneration of nerve damage, both in the peripheral nervous system, and also potentially in the central nervous system.



The peripheral nervous system is made up of all the nerves that branch out from the brain and spinal cord to give us sensation throughout our bodies. There are many cell types in peripheral nerves, here researchers focus on understanding neurons, which transmit information throughout the nervous system, and Schwann cells, which protect healthy neurons and repair damaged ones. The peripheral nervous system’s ability to repair damage is remarkable considering that the central nervous system – made up of the brain and spinal cord – is not able to repair damage. Yet, the mechanisms that orchestrate this feat have remained poorly understood.



To unravel how Schwann cells differentiate to begin repairing peripheral nerve damage, the researchers looked at mouse models of Charcot Marie Tooth disease (CMT), a type of hereditary neuropathy. In mice with CMT, the researchers noticed that the Schwann cells completing repairs had high levels of Mitf in their nuclei – where the genetic instructions for how to be a Schwann cell and how to conduct repairs are stored. Upon investigation of this relationship between Mitf and Schwann cells, they found that Mitf was in the cytoplasm of Schwann cells until sensing neuronal damage. Damage then prompted Mitf to relocate from the cytoplasm of the cell to the nucleus, where it would direct the Schwann cell to make repairs.



To validate the importance of Mitf in creating repair Schwann cells, the researchers removed Mitf altogether. In cases of both trauma and CMT, nerve repair was arrested in the absence of Mitf – demonstrating that Mitf is required for peripheral nerve repair and regeneration. “Harnessing Schwann cell repair programs has great potential in treating chronic diseases. It’s possible that with targeted therapeutics, we can prompt more Schwann cells to repair peripheral nerve damage and push those repairs to completion in chronic cases. Furthermore, now that we have a better grasp on the repair mechanisms, we can see if it’s possible to initiate repairs in the brain stem and spinal cord, too.”


Link: https://www.salk.edu/news-release/repairing-nerve-cells-after-injury-and-in-chronic-disease/

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