Modulating Microglial Activation Through GLP-1 Pathways: A New Frontier in Neuroinflammation Research.

Microglia are the immune cells resident in the central nervous system (CNS) and are involved in CNS homeostasis and in responses to injury and disease. Microglia, upon activation, become pro-inflammatory (M1) or anti-inflammatory (M2), with M1 being neurotoxic and M2 participating in tissue repair. The activation of microglia in neuroinflammation and pain hypersensitivity is important in the neurodegenerative disorders such as Parkinson's (PD) and Alzheimer's disease (AD). Recent investigations have identified GLP-1 receptor agonists (GLP-1 RAs) as potent pharmacological agents that can regulate the activity of the microglia. GLP-1RA attaches to the GLP-1 receptor found on the microglia to cause a phenotypic shift to the anti-inflammatory M2 form, which, in turn, reduces neuroinflammation and increases neuronal protection. Experimental evidence shows that GLP-1 RAs are effective at reducing hypersensitivity to pain, improving cognitive performance, and attenuating inflammatory effects in preclinical models of AD, PD, and multiple sclerosis (MS). All these facts suggest that GLP-1 RAs are a significant treatment option in chronic pain and neurodegenerative disease management, as they can change microglial polarization and suppress neuroinflammation.