By manipulating molecular models, researchers discover protein that could accelerate recovery from peripheral nerve injury.
A team of researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at the University of California Los Angeles (UCLA; CA, USA) have discovered a molecular process that controls the growth rate of nerves during embryonic development and recovery from injury throughout life.
In the study published in the Journal of Neuroscience, the team used mice models to demonstrate the acceleration of peripheral nerve growth caused by manipulating the molecular models.
Peripheral nerve injuries recover slowly and damaged nerves regrow at an average rate of just 1 millimeter per day. This can take a toll on an individual’s life as they may have to live with impaired movement and sensation for many months or years.
“People with severe peripheral nerve injuries often lose sensation, which makes them susceptible to further injury and they lose mobility, which can lead to muscle atrophy,” commented paper author, Samantha Butler (UCLA). “The process of nerve regrowth can be extremely painful and if muscles have atrophied it requires a lot of physical therapy to regain function. My lab seeks methods to accelerate this healing process.”
In a 2010 study, Butler and her colleagues discovered that the rate at which nerves grow in the spinal cord during embryonic development can be controlled by manipulating the activity of a gene called LIM domain Kinase 1 (Limk1). Limk1 controls the rate of nerve growth by regulating the activity of a protein called cofilin, which plays a role in enabling nerves to extend and form neural networks.
Following this, the team of researchers demonstrated that Limk1 and cofilin also control the growth rate of peripheral nerves during both development and regeneration.
“We discovered that one of the first things a nerve does after injury is switch on all these early developmental molecules that controlled how it grew in the first place,” explained Butler. “It’s somewhat similar to how an adult in crisis might reach out to their childhood friends to renew themselves.”
The researchers stated that genetically engineered mice that had the Limk1 gene removed had a 15% increased speed of nerve growth following an injury.
“This is a modest improvement for a mouse but one that could translate into a major improvement for a human because our nerves have so much farther to grow,” added Butler.
The team reported that the increased rate of growth caused faster recovery in both motor and sensory functions, which was shown by the genetically engineered mice regaining their ability to walk faster.
The findings from this study could inform the development of new therapies to reduced recovery time of nerve injuries. Butler and her team plan to use human stem cell-derived motor neurones to screen for potential drug candidates.
Furthermore, they also plan to investigate the effect of adding more cofilin rather than inhibiting Limk1, to assess how effective it is in speeding up nerve injury recovery.
Sources: Frendo ME, da Silva A, Phan KD, Richie S, Butler SJ. The cofilin/Limk1 pathway controls the growth rate of both developing and regenerating motor axons. J. Neurosci. doi:10.1523/JNEUROSCI.0648-19.2019 (2019) (Epub ahead of print); http://newsroom.ucla.edu/releases/molecular-process-accelerates-nerve-injury-recovery