Scientists have found that GLP-1 receptor agonists also suppress brain inflammation, giving them potential "superpowers" in the fight against Alzheimer's and Parkinson's diseases, another surprising property of new obesity drugs. Inflammation is highly prevalent in patients with chronic metabolic diseases and is a hallmark of Alzheimer's and Parkinson's diseases.
"What's really interesting about GLP-1 drugs is that in addition to controlling blood sugar and weight, they appear to reduce the complications of chronic metabolic diseases," said study co-author Daniel Drucker, a professor in the Department of Medicine at the University of Toronto. "We know from clinical studies that GLP-1 can do these amazing things in the body, but we don't fully understand how it works."
Glucagon-like peptide-1 (GLP-1) receptor agonists have become the most watched medical scientific development after mRNA vaccines. Semaglutide and tizapatide, known by brand names including Ozempic, Wegovy, and Mounjaro, were originally used to effectively treat type 2 diabetes but have since risen to prominence as a new, highly regarded weight-loss drug.
Drucker and his team believe that this is not the limit of their "superpowers" and they are very interested in the relationship between inflammation and GLP-1 drugs. Researchers have discovered a new, fascinating and potentially life-changing interaction with other organs, particularly the brain.
"What's strange is that you don't find many GLP-1 receptors in all these other organs where GLP-1 seems to act," Drucker said.
The team found that in mice with inflammation (caused by the immune system's response to bacterial cell wall components or bacterial slurry), GLP-1 agonists reduced the condition, but only when the receptors in the brain were not blocked. This demonstrates a novel way in which GLP-1 drugs interact with inflammation and the brain-immune system axis, independent of their other known benefits.
"While the scientific community is well-deservedly celebrating GLP-1 agonists and their impact, many unknowns remain," said Anne-Claude Gingras, director of the Lunenfeld-Tannenbaum Institute. "This study deepens our understanding of metabolism and the complex immune networks in the brain that regulate it."
In Alzheimer's and Parkinson's diseases, the pathological proteins beta-amyloid and alpha-synuclein each interact with certain receptors to trigger multiple inflammatory pathways. If GLP-1 receptor agonists can be used to modulate the activity of these proteins and receptors, neuroinflammation in these degenerative diseases can be effectively treated.
The team now hopes to identify which brain cells interact with GLP-1 and other models of inflammation in the heart, liver and kidneys, which holds great promise for treating chronic diseases associated with these organs.
The research was published in the journal Cell Metabolism.