TY - JOUR
T1 - Targeting PKC in microglia to promote remyelination and repair in the CNS
AU - Kim, Paul M.
AU - Kornberg, Michael D.
N1 - Funding Information:
This work was supported by grants from Conrad N. Hilton Foundation (Marilyn Hilton Bridging Award for Physician Scientists to M.D.K.), Department of Defense (Multiple Sclerosis Research Program Investigator-Initiated Research Award to P.M.K. and M.D.K.), Maryland Technology Development Corporation (Maryland Innovation Initiative Award to P.M.K. and M.D.K.), and Race to Erase MS (Young Investigator Award to M.D.K.).
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
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U2 - 10.1016/j.coph.2021.11.008
DO - 10.1016/j.coph.2021.11.008
M3 - Review article
C2 - 34965482
AN - SCOPUS:85121783180
SN - 1471-4892
VL - 62
SP - 103
EP - 108
JO - Current Opinion in Pharmacology
JF - Current Opinion in Pharmacology
ER -