Trigger that leads to faster nerve healing

Date:
October 15, 2020
Source:
University of South Carolina
Summary:
Damaged nerves regenerate faster when protein clusters are
broken apart, releasing mRNAs that can be used to rebuild the
nerve. Scientists have found the trigger that could be used to
accelerate regrowth more.



FULL STORY ========================================================================== University of South Carolina scientists are exploring ways to make nerve regeneration happen faster and more successfully.


==========================================================================
A new study published in Current Biology identifies the biological
triggers that promote quicker nerve regeneration. From their previous
studies, the researchers knew that damaged nerves regrow more quickly when "stress granules" in the site of the nerve injury are broken apart. Now
they know what causes those stress granules to disassemble through a
process called protein phosphorylation.

"The important thing is that we identified the protein that drives that
process and showed how that's regulated," Jeff Twiss, a UofSC biology
professor and co- author on the paper, said.

"It actually opens something new," Pabitra Sahoo, the paper's lead
author, said. "In the future, it could help us design molecules that can promote phosphorylation." Twiss said nerves typically regrow at 1 to
2 millimeters per day, meaning that an adult with nerve damage around
their kneecap might require a year to recover as the nerve re-extends
back to the foot. Given such a prolonged time to regenerate the nerve,
atrophy makes a full recovery difficult.

"Finding ways to speed that up is critical to decreasing the amount of
time that a person has loss of function, sensation and movement," said
Twiss, the UofSC SmartState Chair in Childhood Neurotherapeutics. "But
also, when you allow the nerve to find its way back to the target quicker,
you can recover much more function." Nerve cells contain the protein
G3BP1 in clusters known as stress granules.

When a nerve is severed, those granules begin to break apart through phosphorylation, a modification that makes G3BP1 become more negatively charged. This process releases mRNAs, important building blocks that
the cell can use to build new proteins that extend the nerve. This phosphorylation makes the nerve grow faster, according to research that
Sahoo and Twiss's team published in 2018.

The 2020 study took a step back to look for the processes that
trigger the phosphorylation, in hopes that the entire process could be accelerated. The researchers determined that an enzyme known as Casein
kinase 2-alpha (CK2a) is responsible for breaking up the G3BP1 granules
through phosphorylation. When they increased CK2a levels, nerves grew
faster, and the cell contained more phosphorylated G3BP1. When they
decreased CK2a, the process slowed.

But where does the CK2a come from? The researchers placed a piece of
nerve in a test tube, damaged it, and monitored the CK2a levels. Those
levels increased, indicating that the damaged nerve synthesizes CK2a
on its own at the injury site, rather than receiving it from its cell
body. The process seems to be regulated by calcium ions.

These discoveries offer promising areas for further study. The UofSC researchers are already looking at methods for spurring the CK2a synthesis
to speed up the nerve growth. Finding that key could lead to advances
in medicine that result in faster healing after nerve injuries.


========================================================================== Story Source: Materials provided by University_of_South_Carolina. Original written by Bryan Gentry. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Pabitra K. Sahoo, Amar N. Kar, Nitzan Samra, Marco Terenzio,
Priyanka
Patel, Seung Joon Lee, Sharmina Miller, Elizabeth Thames, Blake
Jones, Riki Kawaguchi, Giovanni Coppola, Mike Fainzilber, Jeffery
L. Twiss. A Ca2 -Dependent Switch Activates Axonal Casein Kinase
2a Translation and Drives G3BP1 Granule Disassembly for Axon
Regeneration. Current Biology, 2020; DOI: 10.1016/j.cub.2020.09.043 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201015134212.htm

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