Glucagon-like peptide 1 receptor activation: anti-inflammatory effects in the brain

Abstract

The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and obesity. Glucagon-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues, including different brain regions. Glucagon-like peptide 1 activates several signaling pathways related to neuroprotection, like the support of cell growth/survival, enhancement promotion of synapse formation, autophagy, and inhibition of the secretion of proinflammatory cytokines, microglial activation, and apoptosis during neural morphogenesis. The glial cells, including astrocytes and microglia, maintain metabolic homeostasis and defense against pathogens in the central nervous system. After brain insult, microglia are the first cells to respond, followed by reactive astrocytosis. These activated cells produce proinflammatory mediators like cytokines or chemokines to react to the insult. Furthermore, under these circumstances, microglia can become chronically inflammatory by losing their homeostatic molecular signature and, consequently, their functions during many diseases. Several processes promote the development of neurological disorders and influence their pathological evolution: like the formation of protein aggregates, the accumulation of abnormally modified cellular constituents, the formation and release by injured neurons or synapses of molecules that can dampen neural function, and, of critical importance, the dysregulation of inflammatory control mechanisms. The glucagon-like peptide 1 receptor agonist emerges as a critical tool in treating brain-related inflammatory pathologies, restoring brain cell homeostasis under inflammatory conditions, modulating microglia activity, and decreasing the inflammatory response. This review summarizes recent advances linked to the anti-inflammatory properties of glucagon-like peptide 1 receptor activation in the brain related to multiple sclerosis, Alzheimer's disease, Parkinson's disease, vascular dementia, or chronic migraine.