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Targeting PKC in microglia to promote remyelination and repair in the CNS
Paul M Kim1, Michael D Kornberg2
1Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
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.
Insights
Protein kinase C (PKC) may activate beneficial microglia subtypes for CNS repair. Targeting PKC could offer novel therapies for neurodegenerative diseases like Alzheimer's and Parkinson's.
Area of Science:
- Neuroimmunology
- Neuroinflammation
- Neurodegenerative Diseases
Background:
- Microglia and macrophages are key players in neuroinflammation and neurodegeneration (e.g., Alzheimer's, Parkinson's, MS).
- Dysregulated inflammatory responses by these cells can exacerbate CNS damage, including neurodegeneration and demyelination.
- While pro-inflammatory microglia are detrimental, other subtypes support CNS repair and regeneration.
Purpose of the Study:
- To explore the role of protein kinase C (PKC) in activating reparative/regenerative microglial subtypes.
- To investigate PKC modulators as a potential therapeutic strategy for neuroinflammatory and neurodegenerative diseases.
Main Methods:
- This review focuses on the signaling pathways involving PKC, TREM2, and PLCγ2.
- Literature review of studies investigating microglial function and PKC signaling in CNS diseases.
Main Results:
- PKC is identified as a downstream signaling molecule of TREM2 and PLCγ2.
- PKC signaling is implicated in the activation of beneficial microglial subtypes.
Conclusions:
- Activating reparative/regenerative microglial subtypes via PKC modulation presents a promising therapeutic avenue.
- Targeting PKC may offer novel treatment strategies for conditions such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis.
