Blocking nitric oxide reverses autism-like traits in mice
Mar 8th 2026
Researchers mapped a chain reaction in which nitric oxide S-nitrosylates the TSC2 protein, triggering its destruction and unleashing mTOR-driven cellular overgrowth; blocking nitric oxide restored TSC2, calmed mTOR, and reversed autism-like cellular and behavioral changes in mouse models, with matching signals in human cells and some patient blood samples.
- Nitric oxide chemically tags the TSC2 protein, marking it for degradation by the cell.
- Loss of TSC2 removes a brake on the mTOR pathway, causing excessive protein synthesis in neurons.
- Blocking nitric oxide production preserved TSC2 and normalized mTOR signaling in Shank3 and Cntnap2 mutant mice.
- Treating mutant mice reversed social deficits and anxiety-like behavior in standard behavioral tests.
- Human neurons engineered with a Shank3 mutation and blood samples from some autistic children showed the same TSC2 loss and mTOR overactivity.
- The nitric oxide to TSC2 to mTOR chain offers a clear therapeutic target but requires larger human studies and care because nitric oxide affects many proteins.