Targeting PKC in microglia to promote remyelination and repair in the CNS

Abstract

Microglia and CNS-infiltrating macrophages play significant roles in the pathogenesis of neuroinflammatory and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Prolonged and dysregulated inflammatory responses by these innate immune cells can have deleterious effects on the surrounding CNS microenvironment, which can worsen neurodegeneration and demyelination. However, although chronic activation of pro-inflammatory microglia is maladaptive, other functional microglial subtypes play beneficial roles during CNS repair and regeneration. Therefore, there is a tremendous interest in understanding the underlying mechanism of the activation of these reparative/regenerative microglia. In this review, we focus on the potential role of PKC, a downstream signaling molecule of TREM2 and PLCγ2, and PKC modulators in promoting the activation of reparative/regenerative microglial subtypes as a novel therapy for neuroinflammatory and neurodegenerative diseases.