Professor Stuart Lipton awarded $5 million to study the chemical biology of air pollution on the human brain

The grant from the NIA/NIH will support research into how air pollution could lead to the development of Alzheimer’s disease.

October 01, 2024

LA JOLLA, CA—Stuart Lipton, MD, PhD, professor and Step Family Foundation Endowed Chair, and Tomohiro Nakamura, PhD, Institute Investigator in the Neurodegeneration New Medicines Center and Department of Molecular Medicine at Scripps Research, have been awarded about $5 million from the National Institute on Aging (NIA) to study the impacts of air pollution on the human brain—specifically, how air pollution could contribute to Alzheimer’s disease and related dementias.

The NIA grant will support research over a five-year period as he and his team investigate how pollution sources—including vehicle exhaust, wildfires contribute to a chemical reaction discovered by Lipton referred to as “SNO”—and how this impacts the development of Alzheimer’s disease. NIA, part of the National Institutes of Health (NIH), is focused on expanding our scientific understanding of the nature of aging, improving the health and well-being of older adults, and supporting and conducting research on aging and the challenges and needs of older adults.

“The NIA’s award shows not only how dedicated the organization is to improving human health, but its confidence that Scripps Research has the potential to make an enduring impact on these serious diseases,” Lipton says. 

“SNO” is a reaction that results from exposure to air pollution, which causes nitrogen (N) and oxygen (O) atoms to combine with a sulfur (S) atom on a wide variety of proteins and disrupt their function, resulting in brain damage. This reaction, termed S-nitrosylation, has been observed to cause a “SNO” storm of reactions in Alzheimer’s brain neurons by Lipton and his team. A recent paper from the Lipton group in the journal Science described many of the biochemical pathways affect by the aberrant “SNO” storm in the brain. 

In collaboration with Scripps Research professor John Yates III, PhD, Lipton’s research uses mass spectrometry to discover the proteins that undergo SNO reactions and potentially contribute to the development of Alzheimer’s and other dementias. Identifying these SNO proteins is a critical step in developing new therapeutic targets for diseases, while potentially also helping inform strategies on controlling air pollution.

“Climate change, caused by human actions affecting the composition of air in the atmosphere, has already had a critical impact on global health. It’s vital that we continue to expand this body of research to inform strategies and new therapeutics that address human disease influenced by environmental factors,” Lipton says.

Along these lines, the California Institute of Regenerative Medicine (CIRM) recently made a companion award for Lipton to study the chemical biology of air pollution in autism and intellectual disabilities.

At Scripps Research, Lipton’s lab focuses on investigating molecular signaling pathways in order to prevent neuronal and synaptic injury that occurs as the human body ages, as well as in neurodegenerative diseases like Alzheimer’s, Parkinson’s and other forms of dementia. His research into the drivers of Alzheimer’s disease has already led to real-world results. Lipton is well-known for developing the FDA-approved drug memantine—marketed commercially as Namenda®, Namenda XR®, and Namzaric®—represents one of only two medicines approved to treat moderate-to-severe forms of Alzheimer’s. The drug is also used off-label for other forms of dementia, such as vascular dementia caused by multiple strokes and Lewy body dementia.

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