The drug reduced Aβ42, the largest form of amyloid beta protein found in Alzheimer’s plaques, in mice exposed to air pollution.
RT’s Three Key Takeaways:
- Potential Alzheimer’s Prevention: The investigational drug GSM-15606 reduced levels of the Alzheimer’s-related protein Aβ42 in mice exposed to air pollution, suggesting it may have potential as a preventive measure for people living in polluted environments.
- Targeted Drug Action: GSM-15606 is a gamma-secretase modulator designed to specifically reduce the production of Aβ42 without inhibiting gamma secretase’s normal functions.
- Environmental Health Implications: The study underscores the link between air pollution and increased Alzheimer’s risk, with GSM-15606 offering a possible intervention to mitigate the detrimental effects of air pollution on brain health, particularly in aging populations.
A new study led by the USC Leonard Davis School of Gerontology shows how feeding mice a drug called GSM-15606 provided protection against air pollution-related increases in proteins linked to Alzheimer’s disease.
Senior author Caleb Finch, PhD, USC University professor and holder of the ARCO/William F. Kieschnick Chair in Neurobiology of Aging at the USC Leonard Davis School, has studied air pollution’s effects on the brain for several years, especially the consequences of exposure to fine particulates found in pollution from automobiles, factories, and more.
Many studies have shown that air quality has a sizeable impact on the risk of Alzheimer’s and accelerates cognitive decline, he says. Air pollution is correlated with systemic inflammation and promotes the formation of amyloid plaques, the clumps of aggregated peptide Aβ42 that form between the brain’s nerve cells in Alzheimer’s.
The Protective Role of GSM-15606
The latest work from Finch’s lab, published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, highlights the potential protection offered by a type of drug called a gamma-secretase modulator. The team tested a specific drug called GSM-15606, which was developed by study co-authors Rudolph E. Tanzi, PhD, of Harvard and Kevin D. Rynearson, PhD, of the University of California, San Diego.
GSM-15606 was fed to mice over eight weeks. During that time, the animals were regularly exposed to air pollution in the form of either ambient nanoparticulate matter or diesel exhaust particles. Following air pollution exposure, mice fed GSM-15606 had much lower levels of Aβ42 in the brain than mice exposed to pollution but not the drug.
Future Implications for Alzheimer’s Prevention
The results indicate that GSM-15606 may one day have a role as a preventive measure against Alzheimer’s in people living with air pollution, Finch says.
“Because gamma secretase is needed for normal functions body-wide, this drug was designed to modulate, but not inhibit, production of Aβ42,” he says in a release. “This is the first example of a new drug developed to slow Alzheimer’s that may also protect aging individuals from the environmental risk factor of air pollution.”
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