Myelin Regeneration

Flow chart showing progress of demyelination to remyelination.

High levels of protease-activated receptor (PAR1) signaling promote demyelination, while reduced levels promote myelin repair by fostering the serine/threonine-specific protein kinase AKT and extracellular signal-regulated kinase signaling. Targeting PAR1 represents a new therapeutic target to promote myelin repair in the developing and adult nervous system.

Two electron micrograph panels comparing relative thickness of myelin sheaths in wild-type versus PAR1 knockout mice.

Genetic deletion of PAR1 increases the abundance and thickness of myelin in the adult spinal cord, as cited in Glia, 2015 (Yoon et al.).

Regeneration of myelin in the central nervous system is a crucial area of research. These studies have significant implications for:

  • Treating demyelinating diseases such as multiple sclerosis.
  • Treating neurodegenerative conditions such as Alzheimer's disease.
  • Recovering from spinal cord injuries.

Myelin, the protective sheath around nerve fibers, is essential for the rapid transmission of nerve signals and the health of neurons. When myelin is damaged, it can lead to severe neurological deficits. However, the central nervous system has a limited capacity for myelin repair, which has sparked interest in understanding and enhancing this process.

Recent studies from Dr. Scarisbrick's Neuroregeneration and Neurorehabilitation Laboratory demonstrated that aberrant protease signaling at protease-activated receptor 1 (PAR1), or PAR2, promotes demyelination. PAR1 and PAR2 also actively suppresses the differentiation of oligodendrocyte precursor cells, which are the mediators of both developmental myelination and innate myelin regeneration in adults. The lab's team is investigating the roles of these G protein-coupled receptors in glial biology, including myelination and remyelination, to identify novel targets for therapy to improve functional outcomes.

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