Protease Activated Receptor 1 and Its Ligands as Main Regulators of the Regeneration of Peripheral Nerves

Biomolecules, 2021 · DOI: https://doi.org/10.3390/biom11111668 · Published: November 10, 2021

Simple Explanation

Peripheral nerves can regenerate after damage, unlike the brain and spinal cord. This is mainly due to Schwann cells, glial cells that activate upon nerve injury to assist axon regrowth. Tissue injury releases proteases that activate protease-activated receptors (PARs). PAR1, a thrombin receptor on Schwann cells, is emerging as a regulator of Schwann cell pro-regenerative capacity. This review summarizes recent literature on PAR1 and PAR1-activating proteases and their role in regulating peripheral nerve regeneration.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Low levels of thrombin enhance peripheral nerve regeneration after crush injury, whereas high concentrations have detrimental effects.
2
PAR1 activation with high concentrations of thrombin causes a conduction block in motor nerve fibers.
3
The analysis of the possible role of PAR1 in regulating the regenerative processes in peripheral nerve injury gets further complicated by the possible involvement of other PAR1 agonists different from thrombin.

Research Summary

The review focuses on how thrombin modulates Schwann cell pro-regenerative capacities through PAR1 after peripheral nerve injury. Besides thrombin, other proteases like FXa, FVIIa, APC, plasmin, and MMPs can also cut and signal through PAR1. Optimal nerve regeneration requires finely tuned stimulation of glial PAR1, as excessive PAR1/thrombin axis activation could limit Schwann cell trophic support.

Practical Implications

Therapeutic Potential

Pharmacological inhibition of PAR1 activation could restore Schwann cell pro-regenerative functions and promote nerve functional recovery.

Further Research Needed

Future studies are necessary to clarify the complex regulation of different PAR1-activating proteases in modulating peripheral nerve regeneration.

Clinical Relevance

Understanding the role of PAR1 in peripheral nerve regeneration may lead to improved treatments for nerve injuries, paralysis, and chronic pain.

Study Limitations

1
The repair SC phenotype is unstable and fades with time in the chronically denervated distal stump.
2
The pro-survival activity of repair SCs tends to decline with aging.
3
There are currently no treatments to successfully foster myelin regeneration after injury of the PNS.

Your Feedback

Was this summary helpful?

Back to Neurology