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UofSC scientists identify biological triggers that promote faster nerve regeneration

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Scientists at the University of South Carolina are looking for ways to make nerve regeneration faster and more successful.

New research published in Current biology Identify biological triggers that promote faster nerve regeneration. From their previous studies, researchers knew that when the “stress granules” at the site of nerve damage fell apart, the damaged nerve regrown faster.Now they know what causes those stress granules to break down through a process called Protein phosphorylation..

The important thing is to identify the proteins that drive the process and show how they are regulated. “

Jeff Twis, Professor of Biology at UofSC and co-author of the dissertation

“It really opens up something new,” said Pavitra Sahu, the lead author of the paper. “In the future, it may help in the design of molecules that can promote phosphorylation.”

According to Twis, nerves usually re-grow at 1-2 millimeters per day. This means that an adult with nerve damage around the patella may take a year to recover as the nerve returns to the foot. Given such a long time to regenerate nerves, atrophy makes complete recovery difficult.

“Finding a way to speed it up is important to reduce the amount of time a person loses function, sensation, or movement,” said Twiss, the UofSC SmartState chair in Child Neurology. “But also, allowing nerves to return to their targets faster can restore much more function.”

Nerve cells contain the protein G3BP1 in clusters known as stress granules. When the nerve is cut, these granules begin to break down by phosphorylation. This causes G3BP1 to become more negatively charged. This process releases mRNA, an important component that cells can use to build new proteins that stretch nerves. This phosphorylation accelerates nerve growth, according to a study published in 2018 by the Sahoo and Twiss team.

The 2020 study took a step back to look for processes that cause phosphorylation, hoping that the entire process would be accelerated. Researchers have determined that an enzyme known as casein kinase 2-alpha (CK2α) is responsible for the degradation of G3BP1 granules by phosphorylation. As they increased CK2α levels, nerves grew faster and cells contained more phosphorylated G3BP1. The process slowed down when they reduced CK2α.

But where did CK2α come from? Researchers monitored some of the nerves by placing them in test tubes and damaging them, and monitoring CK2α levels. These levels increase, indicating that the injured nerve does not receive CK2α from the cell body, but synthesizes itself at the site of injury. This process seems to be regulated by calcium ions.

These discoveries provide a promising area for further research. UofSC researchers are already looking at ways to stimulate CK2α synthesis and accelerate nerve growth. Finding the key can lead to medical advances that result in faster healing after nerve injury.

Source:

Journal reference:

Sahoo, PK, et al. (2020) A Ca2+-Dependent switches activate translation of axonal casein kinase 2α and promote G3BP1 granulation degradation for axonal regeneration. Current biology. doi.org/10.1016/j.cub.2020.09.043..

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