Myelin Regeneration

Regeneration of myelin in the central nervous system (CNS) is a crucial area of research. These studies have significant implications for treating demyelinating diseases such as multiple sclerosis, for neurodegenerative conditions such as Alzheimer's disease, and for recovery from spinal cord injuries. Myelin, the protective sheath around nerve fibers, is essential for the rapid transmission of nerve signals and for the health of neurons. When myelin is damaged, it can lead to severe neurological deficits. However, the CNS 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 (OPCs), which are the mediators of both developmental myelination and of 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.

Related publications

• Cerebrospinal fluid camk2a levels at baseline predict long-term progression in multiple sclerosis.
• Quantitation of neurofilament light chain protein in serum and cerebrospinal fluid from patients with multiple sclerosis using the MSD R-PLEX NfL assay.
• Blocking Kallikrein 6 promotes developmental myelination.
• Blocking the thrombin receptor promotes repair of demyelinated lesions in the adult brain.
• Protease-activated receptor 2 controls myelin development, resiliency and repair.
• The thrombin receptor is a critical extracellular switch controlling myelination.
• Differential expression of multiple kallikreins in a viral model of multiple sclerosis points to unique roles in the innate and adaptive immune response.
• Critical role for PAR1 in kallikrein 6-mediated oligodendrogliopathy.
• Activation profiles of human kallikrein-related peptidases by matrix metalloproteinases.
• Kallikrein 6 regulates early CNS demyelination in a viral model of multiple sclerosis.
• Kallikrein 6 is a novel molecular trigger of astrogliosis.
• Functional role of kallikrein 6 in regulating immune cell survival.
• Functional intersection of the kallikrein-related peptidases (KLKs) and thrombostasis axis.
• Activation profiles of human kallikrein-related peptidases by proteases of thrombostasis axis.
• Protease-activated receptor dependent and independent signaling by kallikreins 1 and 6 in CNS neuron and astroglial cell lines.
• Kallikreins are associated with secondary progressive multiple sclerosis and promote neurodegeneration.
• The multiple sclerosis degradome: Enzymatic cascades in development and progression of central nervous system inflammatory disease.
• Potential scope of action of tissue kallikreins in CNS immune-mediated disease.
• Kallikrein-mediated cell signaling: Targeting proteinase-activated receptors (PARs).
• Substrate specificity of human kallikrein 6: Salt and glycosaminoglycan activation effects.
• Distinct promoters regulate tissue-specific and differential expression of kallikrein 6 in CNS demyelinating disease.
• Targeting kallikrein 6-proteolysis attenuates CNS inflammatory disease.
• Hit-hit and hit-run: Viruses in the playing field of multiple sclerosis.
• Crystal structure and biochemical characterization of human kallikrein 6 reveals that a trypsin-like kallikrein is expressed in the central nervous system. 
• Enzymatic properties of rat myelencephalon-specific protease. 
• Activity of a newly identified serine protease in CNS demyelination.
• MSP, a trypsin-like serine protease, is abundantly expressed in the human nervous system.
• Preferential expression of myelencephalon-specific protease by oligodendrocytes of the adult rat spinal cord white matter.
• Nervous system-specific expression of a novel serine protease: Regulation in the adult rat spinal cord by excitotoxic injury.