A new study led by the USC Leonard Davis School of Gerontology shows how feeding mice a drug called GSM-15606 protected against air pollution-induced increases in proteins linked to Alzheimer’s disease.
Senior author Caleb Finch, a USC University professor and holder of the ARCO/William F. Kieschnick Chair in the Neurobiology of Aging at the USC Leonard Davis School, has spent years studying the effects of air pollution on the brain, especially the effects of exposure to fine particles. particles found in pollution from cars, factories and more. Many studies have shown that air quality has a significant impact on Alzheimer’s risk and accelerates cognitive decline, he said.
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 disease.
The latest work from Finch’s lab, published August 12 Alzheimer’s and Dementia: The Journal of the Alzheimer’s Associationhighlights the potential protection provided by a type of drug called a gamma-secretase modulator. The team tested a specific drug called GSM-15606, which was developed by co-authors Rudolph E. Tanzi of Harvard and Kevin D. Rynearson of the University of California, San Diego.
GSM-15606 was fed to mice for 8 weeks; during that time, the animals were regularly exposed to air pollution in the form of environmental nanoparticles (nPM) or diesel exhaust particles (DEP). After exposure to air pollution, mice given GSM-15606 had much lower levels of Aβ42 in the brain than mice exposed to pollution but not the drug.
The results indicate that GSM-15606 may one day play a role as a preventive measure against Alzheimer’s disease in people living with air pollution, Finch said.
Because gamma secretase is necessary for normal body functions, this drug is designed to modulate, but not inhibit, the production of Aβ42. This is the first example of a new drug designed to slow Alzheimer’s disease that may also protect older people from the environmental risk factor of air pollution.”
Caleb Finch, USC University Professor and holder of the ARCO/William F. Kieschnick Chair in the Neurobiology of Aging at the USC Leonard Davis School
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Magazine reference:
Godoy-Lugo, JA, et al. (2024). Air pollution amyloidogenesis is attenuated by the gamma-secretase modulator GSM-15606. Alzheimer’s and dementia. doi.org/10.1002/alz.14086.