TRPV2: A Key Player in Myelination Disorders of the Central Nervous System

Abstract

Transient potential receptor vanilloid 2 (TRPV2) is widely expressed through the nervous system and specifically found in neuronal subpopulations and some glial cells. TRPV2 is known to be sensitized by methionine oxidation, which results from inflammation. Here we aim to characterize the expression and regulation of TRPV2 in myelination pathologies, such as hypomyelination and demyelination. We validated the interaction between TRPV2 and its putative interactor Opalin, an oligodendrocyte marker, in mixed glial cultures under pro- and anti-inflammatory conditions. Then, we characterized TRPV2 time-course expression in experimental animal models of hypomyelination (jimpy mice) and de-/remyelination (cuprizone intoxication and experimental autoimmune encephalomyelitis (EAE)). TRPV2 showed upregulation associated with remyelination, inflammation in cuprizone and EAE models, and downregulation in hypomyelinated jimpy mice. TRPV2 expression was altered in human samples of multiple sclerosis (MS) patients. Additionally, we analyzed the expression of methionine sulfoxide reductase A (MSRA), an enzyme that reduces oxidated methionines in TRPV2, which we found increased in inflammatory conditions. These results suggest that TRPV2 may be a key player in myelination in accordance with the recapitulation hypothesis, and that it may become an interesting clinical target in the treatment of demyelination disorders.

Human brain aging heterogeneity observed from multi-region omics data reveals a subtype closely related to Alzheimer’s disease

“…Studies have shown TRPV2 regulation during inflammation in microglia and immune cells, as well as during remyelination in oligodendrocytes. TRPV2 has been suggested as an interesting clinical target for the development of therapeutic interventions for myelination disorders[48]. GSTM3 colocalizes with amyloid-beta plaques in AD and reduces antioxidant defense.…”

Roles of TRP and PIEZO receptors in autoimmune diseases

“…The findings suggest that TRPV2 may play a key role in myelination and could be an interesting clinical target for the treatment of demyelinating diseases (Ref. 55).…”

Micromotion Derived Fluid Shear Stress Mediates Peri‐Electrode Gliosis through Mechanosensitive Ion Channels

“…Recently, mechanosensitive (MS) ion channels have come to the forefront of neuromechanobiology and have been shown to undergo activation or differential expression in response to mechanical stimuli within the CNS, [32] with important functions in blood-brain barrier maintenance, [33] neural differentiation, [34,35] nociception, [36][37][38] neural-glia communication, [39] and glia activation. [40][41][42][43][44][45] Critically, MS channel expression is perturbed in neurodegenerative disorders [46] including Alzheimer's disease, [45,47] myelination disorders, [48][49][50] migraine, [51][52][53] and glioma. [54][55][56] In order to gain insight into the role of cyclic mechanical forces in the onset and evolution of peri-electrode gliosis, recent studies have described the development of cell culture models, which mimic physiologically relevant neuroelectrode micromotions and which have demonstrated partial success in reproducing the processes of gliosis in vitro.…”