Uncovering the Link Between Air Pollution and Alzheimer’s: How Toxins in the Air Impact Brain Health
Air pollution contributes to nearly 7 million premature deaths each year, with effects extending beyond just the lungs. Breathing in pollutants from sources like wildfire smoke and city smog can increase the risk of asthma, heart disease, and now, according to new research, brain conditions such as Alzheimer’s and autism.
Scientists at Scripps Research have uncovered how a chemical change in the brain, known as S-nitrosylation, disrupts normal brain cell function. This change, triggered by inflammation, aging, and exposure to toxins found in air pollution, pesticides, wildfire smoke, and processed meats, prevents brain cells from forming new connections and ultimately leads to cellular death.
Published in the Proceedings of the National Academy of Sciences on February 27, 2025, the research showed that blocking S-nitrosylation in a key brain protein partially reversed signs of memory loss in Alzheimer’s mouse models and human stem cell-derived nerve cells.
Senior author and professor Stuart Lipton, MD, PhD, explained, “We’ve revealed the molecular details of how pollutants can contribute to memory loss and neurodegenerative disease. This could lead to new drugs that block these effects to better treat Alzheimer’s disease.”
Lipton first discovered S-nitrosylation over two decades ago, a process where a molecule related to nitric oxide binds to sulfur atoms within proteins, altering their function. Excess nitric oxide, produced in response to pollutants like small particulate material and nitrate-related compounds found in air pollution, can lead to aberrant S-nitrosylation reactions linked to various conditions including cancer, autism, and neurodegenerative diseases.
In the recent study, Lipton’s team investigated the impact of S-nitrosylation on the protein CRTC1, crucial for forming and maintaining connections between brain cells essential for learning and memory. Excess nitric oxide was found to lead to S-nitrosylation of CRTC1, preventing it from binding to another critical brain regulatory protein, CREB, and inhibiting the stimulation of genes necessary for neuron connections.
The researchers genetically engineered a version of CRTC1 resistant to S-nitrosylation, which when introduced into human nerve cells derived from Alzheimer’s patients, prevented disease symptoms and restored memory-related gene activation in mouse models.
Lipton emphasized the potential of targeting S-nitrosylation to treat Alzheimer’s and other neurological diseases, especially as environmental toxins can elevate nitric oxide levels in the brain, accelerating brain aging and disease progression.
The study’s findings shed light on the role of S-nitrosylation in Alzheimer’s disease and aging-related brain damage, offering a potential pathway for developing new treatments. Lipton’s team is now focused on developing drugs to selectively block harmful S-nitrosylation reactions, including those affecting CRTC1.
The study, “S-Nitrosylation of CRTC1 in Alzheimer’s disease impairs CREB-dependent gene expression induced by neuronal activity,” was authored by Xu Zhang, Roman Vlkolinsky, Chongyang Wu, Nima Dolatabadi, Henry Scott, Andrew Zhang, Mayra Blanco, Nhi Lang, Juan Piña-Crespo, Tomohiro Nakamura, Marisa Roberto, and Olga Prikhodko. Funding was provided by the California Institute for Regenerative Medicine and the National Institutes of Health.