March 7, 2026 – Jerusalem, Israel – Researchers at the Hebrew University of Jerusalem have discovered a molecular chain reaction in the brain that may play a role in some forms of autism. The study highlights how the signaling molecule nitric oxide can sometimes disrupt key cellular systems, offering new insights into autism biology and potential treatments.
Nitric oxide is a tiny molecule that usually helps brain cells communicate. It fine-tunes signals between neurons, keeping brain networks responsive. However, the new study suggests that in certain cases of autism spectrum disorder (ASD), rising nitric oxide levels can act like a “stuck button,” triggering a cascade of changes inside neurons.
The researchers found that this chain reaction affects a protective protein called TSC2. Under normal conditions, TSC2 acts as a brake on the mTOR pathway, a system that controls cell growth and protein production. When nitric oxide modifies TSC2, the protein weakens and mTOR activity can become overactive. Excessive mTOR signaling may interfere with how neurons function and communicate.
“Our results suggest that a single molecular change can disrupt a major cellular control system in the brain,” said Prof. Haitham Amal, the Satell Family Professor of Brain Sciences at the Hebrew University of Jerusalem.
The team tested ways to interrupt this pathway. Using drugs to reduce nitric oxide production in neurons, they found that TSC2 levels remained stable and mTOR activity returned to normal. In a complementary approach, they engineered a version of TSC2 resistant to nitric oxide modification, which also helped restore balance in the cells.
These findings suggest a potential target for therapies aimed at restoring normal cellular signaling in autism.
The researchers also studied samples from children with ASD, including those with SHANK3 mutations and idiopathic cases without known genetic causes. They observed reduced TSC2 levels and overactive mTOR signaling, consistent with the lab findings.
“Autism is not one condition with one cause,” Prof. Amal said. “But by tracing this chain of events, we can map a clearer path for research and potential treatments.”
The study highlights the importance of the nitric oxide-TSC2-mTOR connection in understanding ASD. It may guide the development of targeted interventions and provide a framework for future research on how brain cell signaling becomes unbalanced in autism.
ASD is a neurodevelopmental condition affecting social communication and behavior. Researchers continue to investigate pathways like mTOR, which regulate brain cell growth and connectivity, as potential avenues for new treatments.
