A study published in Aging-US on March 29, 2025, reveals promising advances in Alzheimer’s disease (AD) treatment. Led by Sultan Darvesh from Dalhousie University, the research focuses on the use of senolytics—compounds that target and eliminate damaged or “zombie” cells, which accumulate with aging and contribute to inflammation and tissue dysfunction.
The study investigates how senolytics can specifically target harmful brain enzymes involved in Alzheimer’s disease without affecting healthy enzymes, offering a potential path toward more precise treatments. Alzheimer’s is marked by amyloid-beta plaques in the brain, which interact with two enzymes—acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). These enzymes are important for brain function, but their interaction with plaques contributes to AD progression. Current treatments targeting these enzymes often block both harmful and normal forms, causing unwanted side effects.
In their research, the team tested six compounds known for their anti-aging or cognitive-enhancing properties. They discovered that senolytic compounds like dasatinib and nintedanib selectively blocked the forms of AChE and BChE associated with amyloid-beta plaques, while sparing the normal, healthy enzymes. This selectivity could lead to therapies that better preserve memory and reduce brain inflammation, with fewer side effects.
The study also employed computer modeling to explore how these compounds interact with the enzymes. The models showed that the enzymes near amyloid plaques undergo structural changes, which make them easier targets for the senolytics. This mechanism could explain why certain compounds are able to specifically target the diseased areas of the brain.
These findings suggest a novel approach to treating Alzheimer’s disease by targeting the differential forms of enzymes in diseased versus healthy brain regions. This targeted therapy could improve treatment outcomes and reduce adverse effects associated with current medications.
In conclusion, this research offers new hope for the development of more precise, effective treatments for Alzheimer’s disease, highlighting the intersection of aging research and neurodegenerative disease treatment.
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