Genes undergo extensive editing through a process called alternative splicing, which greatly increases the size of the functional genome. A functional genome is the functional part of DNA that helps make each person unique. Simply put, a single gene can be edited in different ways to generate multiple sets of instructions.
This helps explain why humans are so different from fruit flies and mice, even though they have the same number of genes.
In a new study published on May 21, 2026, molecular cell, Researchers at University Hospitals and Case Western Reserve University have discovered that nitric oxide, a gas naturally produced in the body, can broadly regulate alternative splicing and dramatically alter the function of genes.
They also showed that nitric oxide levels are reduced in the brains of Alzheimer’s patients, and that this loss of gene splicing control correlates with worse clinical outcomes. In other words, lower nitric oxide levels reduce gene splicing activity, which is associated with increased plaque accumulation and more rapid memory loss. ”
Jonathan Stamler, MD, lead study author, director and co-founder of the Harrington Discovery Institute at University Hospitals
Mr. Stamler is a Distinguished University Professor at Case Western Reserve School of Medicine and the Robert S. Reitman and Sylvia K. Reitman Family Foundation Chair in Cardiovascular Innovation.
The researchers also discovered that a specific enzyme removes nitric oxide from brain proteins that regulate splicing, creating a state of nitric oxide deficiency. The findings suggest that targeting these enzymes may represent a new therapeutic strategy to restore nitric oxide levels in the brain and treat Alzheimer’s disease.
“Interestingly, in the Alzheimer’s disease field, it has long been believed that nitric oxide levels are too high and contribute to Alzheimer’s disease,” Dr. Stamler added. “This new discovery changes that paradigm.”
Next steps in this research will include studies in animals with a new class of enzyme inhibitors that restore nitric oxide in the brain and promote healthy splicing of genes.
This new class of medicines will be developed with support from the University of California Harrington Discovery Institute, which has the sole mission of accelerating the discovery of promising medicines that address unmet needs. Now in its 13th year, Harrington Discovery Institute’s portfolio has expanded to include 239 medicines currently in development. Supported by 75 institutions. 46 companies were launched. 28 types of medicines in the clinic. 15 pharmaceutical licenses.
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Reference magazines:
Schindler, J.C.; others (2026). Nitric oxide drives proteomic diversity through alternative splicing. molecular cell. DOI: 10.1016/j.molcel.2026.04.024. https://www.cell.com/molecular-cell/fulltext/S1097-2765(26)00278-9.
