In a May 2025 Nature Aging publication, Zhang and colleagues report that GLP-1 receptor agonists (GLP-1R agonists), widely used in the treatment of type 2 diabetes, may also alleviate Alzheimer’s disease (AD) symptoms in mice.
Key Findings
The study demonstrates that GLP-1R agonists act on multiple brain cell types and contribute to neuroprotection through:
- Activation of the AMPK signaling pathway
- Enhancement of neuronal amyloid-β metabolism
- Promotion of microglial phagocytosis
These mechanisms collectively reduced amyloid pathology and improved cognitive performance in animal models.
Repurposing GLP-1R Agonists
Originally developed for diabetes and obesity, GLP-1R agonists have gained attention for their neuroprotective properties, with increasing research into their potential application in Alzheimer’s and Parkinson’s disease.
Connecting Energy Metabolism and Brain Aging
Age-related changes in energy regulation have been implicated in neurodegeneration. GLP-1 signaling may offer a way to restore metabolic balance in the brain, hinting at rejuvenative potential through cellular energy remodeling.
Outlook and Challenges
Although these findings are limited to mouse models, the existing clinical use of GLP-1R agonists could accelerate translational research and clinical trials in human neurodegenerative conditions.
Source: Na D, Schneeberger Pané M. GLP-1R agonists protect against Alzheimer’s disease by rewiring energy regulation. Nature Aging. May 20, 2025. Read Article
Related Article: AMPK activation by GLP-1R agonists mitigates Alzheimer-related phenotypes (Nature Aging, May 2025)
【My Thoughts】
GLP-1R agonists, once considered purely metabolic drugs, may soon play a central role in addressing age-related neurodegeneration. Their dual effects on glucose control and brain function open promising avenues for both disease treatment and healthy aging.
Comments