Researchers give insight into repairing nerve cells after injury, in chronic disease

Every year, over 3 million individuals in the United States experience peripheral neuropathy, a state in which nerves outside of the brain and spinal cord are damaged, causing discomfort and loss of sensation in the affected regions. Diabetes, traumas, inherited genetic conditions, infections, and various other factors can all lead to peripheral neuropathy.

Experts at Salk have unveiled a technique in mice for restoring injured nerves during peripheral neuropathy. They ascertained that the protein Mitf facilitates the activation of the restoration function of specialized Schwann cells in the nervous system.
The discoveries, set to be published in Cell Reports, have the potential to inspire innovative treatments that enhance the restoration function and mend peripheral neuropathy.
“We were curious about the mechanisms governing the response to damage in peripheral nerves under different conditions – such as acute trauma, genetic disorders, or degenerative ailments,” explained senior author Professor Samuel Pfaff. “We discovered that Schwann cells, which are specific cells in nerves that shield and support neurons’ axons, enter their restoration state due to a pathway controlled by the protein Mitf.”
The peripheral nervous system comprises all the nerves that extend from the brain and spinal cord to provide us with sensation throughout our bodies. There are numerous cell types in peripheral nerves, but Pfaff and his team concentrate on comprehending neurons, which transmit information throughout the nervous system, and Schwann cells, which protect healthy neurons and mend damaged ones.
The capability of the peripheral nervous system to mend damage is astounding given that the central nervous system – composed of the brain and spinal cord – is incapable of repairing damage. Nevertheless, the mechanisms orchestrating this accomplishment have remained poorly comprehended.
To decipher how Schwann cells transform to commence mending peripheral nerve damage, the researchers examined mouse models of Charcot Marie Tooth disease (CMT), a form of hereditary neuropathy.
“Entering into this project, I assumed that in cases of genetic nerve degenerative disorders, cells are perishing and recuperation is not viable,” stated first author Lydia Daboussi, a former postdoctoral researcher in Pfaff’s laboratory and presently an assistant professor at UC Los Angeles. “However, our findings demonstrate that there are genetic programs activated by Mitf that mend some of the damage caused in those persistent disease scenarios, and upon deactivating those programs, disease symptoms exacerbate.”
In CMT-afflicted mice, the researchers observed that the Schwann cells completing the repairs exhibited elevated levels of Mitf in their nuclei – where the genetic directives for how to be a Schwann cell and how to carry out repairs are stored.
Upon investigating this association between Mitf and Schwann cells, they found that Mitf remained in the cytoplasm of Schwann cells until it detected neuronal damage. Subsequently, the damage prompted Mitf to relocate from the cell’s cytoplasm to the nucleus, where it would instruct the Schwann cell to carry out repairs.
In order to confirm the significance of Mitf in generating repair Schwann cells, the researchers eliminated Mitf entirely. Consequently, in cases of both trauma and CMT, nerve repair was arrested in the absence of Mitf – indicating that Mitf is essential for peripheral nerve repair and regeneration.
According to Daboussi, Mitf functions akin to a fire extinguisher. Always present, residing in the Schwann cell, unnoticed until damage occurs. And once the damage occurs, Mitf is prepared and immediately activates the cell’s repair functions.
Pfaff remarked that the most surprising aspect was that Mitf was coordinating these repairs during a chronic disease like CMT.
“Capitalizing on Schwann cell repair programs holds substantial potential in managing persistent diseases,” stressed Pfaff, who also holds the Benjamin H. Lewis Chair at Salk. “It’s feasible that with specific therapeutics, we can prompt more Schwann cells to mend peripheral nerve damage and drive those repairs to completion in chronic cases. Additionally, now that we have a better understanding of the repair mechanisms, we can explore the feasibility of initiating repairs in the brain stem and spinal cord as well.” (ANI)