Jerusalem, 8 March, 2026 (TPS-IL) — Israeli scientists say they have identified a biological process that may help explain how certain brain signals become disrupted in some forms of autism spectrum disorder, offering a possible new direction for future treatments.
Autism spectrum disorder is a neurodevelopmental condition that affects social communication and behavior. It involves a wide range of genetic and biological factors. Recent estimates suggest roughly 1 in 100 people globally are on the autism spectrum, representing more than 60 million individuals. While the biological pathway identified in the new study may apply only to some forms of autism, the findings could eventually help guide treatments for a significant subset of those millions of people living with the condition.
The study, published in the peer-reviewed journal Molecular Psychiatry, examines the role of nitric oxide, a small chemical messenger that normally helps brain cells communicate with one another.
Under typical conditions, nitric oxide plays a helpful role by fine-tuning signals between neurons. But the researchers found that in some forms of autism, increased nitric oxide may trigger a chain reaction that disrupts an important cellular control system.
The research was led by Prof. Haitham Amal, The Satell Family Professor of Brain Sciences at the Hebrew University of Jerusalem, and first-authored by doctoral student Shashank Ojha. The team focused on the interaction between nitric oxide, a protective protein called TSC2, and the mTOR pathway, which regulates how cells grow and produce proteins.
Scientists have long suspected that the mTOR pathway can become overactive in autism. However, the biological steps leading to that change have not been clearly understood.
The researchers studied a chemical process called S-nitrosylation, which occurs when nitric oxide attaches to proteins and changes how they behave. Their analysis showed that proteins linked to the mTOR pathway were strongly affected by this process.
One of the key proteins involved is TSC2, which normally acts as a brake that keeps mTOR activity under control. The researchers found that nitric oxide can modify TSC2 in a way that marks it for removal from the cell.
When TSC2 levels drop, the brake on the mTOR system weakens. As a result, mTOR activity can rise to unusually high levels. Because this pathway helps control protein production and other essential cell functions, such changes may affect how brain cells operate and communicate.
The team then tested whether stopping this process could restore balance. By using drugs that reduce nitric oxide production in neurons, the researchers were able to prevent the modification of TSC2 and bring mTOR activity back to more normal levels.
The intervention also improved measures linked to abnormal protein production and other indicators associated with autism in the experimental system.
In another experiment, the scientists engineered a version of the TSC2 protein that resists nitric oxide-related modification. Preventing that single chemical change helped protect TSC2 levels and reduced the effects of excessive mTOR activity.
The researchers also examined clinical samples from children with autism spectrum disorder. The group included children with SHANK3 gene mutations as well as children with idiopathic autism, meaning cases without a single known genetic cause. The samples were collected by Dr. Adi Aran.
According to the researchers, the samples showed signs consistent with the proposed mechanism, including reduced TSC2 levels and increased activity in the mTOR pathway.
“Autism is not one condition with one cause, and we don’t expect one pathway to explain every case,” Amal said. “But by identifying a clearer chain of events, how nitric oxide-related changes can affect a key regulator like TSC2 and, in turn, mTOR, we hope to provide a more precise map for future research and, eventually, more targeted therapeutic ideas.”
By mapping how nitric oxide affects TSC2 and mTOR, the study provides a concrete model of how cellular signaling can go off balance in autism.
The findings open a door to targeted therapies and identifying measurable biomarkers. Future therapies could aim to reduce excessive nitric oxide signaling or protect TSC2 from being altered, helping restore normal cell function in the brain. Reduced levels of TSC2 or signs of overactive mTOR signaling may help doctors identify which individuals.
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