Kinase-based taming of brain microglia toward disease-modifying therapy

Abstract

Microglia are the primary immune cells residing in the central nervous system (CNS), where they play essential roles in the health and disease. Depending on the CNS inflammatory milieu, they exist in either resting or activated states. Chronic neuroinflammation mediated by activated microglia is now considered to be a common characteristic shared by many neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis, which currently pose a significant socioeconomic burden to the global healthcare system. Accumulating evidence has indicated protein kinases (PKs) as important drug targets for therapeutic interventions of these detrimental diseases. Here, we review recent findings suggesting that selected PKs potentially participate in microglia-mediated neuroinflammation. Taming microglial phenotypes by modulating the activity of these PKs holds great promise for the development of disease-modifying therapies for many neurodegenerative diseases.