Protease Activated Receptor 2 Controls Myelin Development, Resiliency and Repair

Glia, 2017 · DOI: 10.1002/glia.23215 · Published: December 1, 2017

Simple Explanation

This research investigates how a specific receptor, called protease-activated receptor 2 (PAR2), affects the development and repair of myelin, the protective coating around nerve fibers, using the spinal cord as a model. The study found that when PAR2 is absent, myelin production accelerates, leading to higher levels of myelin-related proteins and thicker myelin sheaths. This effect is linked to increased numbers of oligodendrocytes, the cells that produce myelin. The study also suggests that PAR2 activation reduces myelin production, and that blocking PAR2 could help protect myelin after spinal cord injury and promote its regeneration after demyelination.

Study Duration

Not specified

Participants

Mice genetically deficient in PAR2 (PAR2-/-) and PAR2+/+ littermates

Evidence Level

Not specified

Key Findings

1
Genetic deletion of PAR2 accelerates myelin production, resulting in higher levels of myelin-related proteins and thicker myelin sheaths.
2
PAR2 loss-of-function increases the number of oligodendrocytes and elevates cAMP and ERK1/2 signaling.
3
PAR2 knockout mice exhibit improved myelin resiliency after traumatic spinal cord injury and accelerated myelin regeneration after focal demyelination.

Research Summary

This study identifies PAR2 as a key regulator of myelin development, resiliency, and regeneration in the central nervous system (CNS). The absence of PAR2 leads to increased myelin production during development and after demyelination, suggesting that PAR2 acts as an innate suppressor of myelin production. The findings suggest that PAR2 is uniquely positioned as a target for therapies aimed at improving myelin production, preservation, and regeneration in both developing and adult CNS.

Practical Implications

Therapeutic Target

PAR2 is a potential new drug target to promote myelin protection and repair.

Drug Development

PAR2 small molecule inhibitors have therapeutic potential for conditions affecting myelin development and regeneration.

Treatment Strategies

Blocking PAR2 may be a novel approach to enhancing myelin resiliency and myelin regeneration in the adult spinal cord.

Study Limitations

1
The study used mice with complete PAR2 knockout, limiting the ability to address cellular mechanisms specifically.
2
PAR2 is expressed by other cell types besides oligodendrocytes, so the observed effects may not be solely due to changes in myelinating cells.
3
PAR2 is widely distributed in peripheral organs, and the study does not differentiate between CNS-specific and systemic effects of PAR2 knockout.

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