Nitrosative Stress in Autism: Supportive Evidence and Implications for Mitochondrial Dysfunction

Richard E. Frye*, Shannon Rose, Irena Voinsky, David Gurwitz*

*Corresponding author for this work

Research output: Contribution to journalComment/debate


A recent study by the Amal team published in this journal in May 2023 proved for the first time the link of nitric oxide (NO) with autism spectrum disorder (ASD), thereby opening new venues for the potential use of neuronal nitric oxide synthase (nNOS) inhibitors as therapeutics for improving the neurological and behavioral symptoms of ASD. The authors conclude that their findings demonstrate that NO plays a significant role in ASD. Indeed, earlier studies support elevated NO and its metabolites, nitrite, and peroxynitrite, in individuals diagnosed with ASD. Dysregulated NOS activity may underlie the well-documented mitochondrial dysfunction in a subset of individuals with ASD. Strategies for treating ASD shall also consider NO effects on mitochondrial respiration in modulating NOS activity. Further experimental evidence and controlled clinical trials with NOS modifiers are required for assessing their therapeutic potential for individuals with ASD.

Original languageEnglish
Article number2304439
JournalAdvanced Science
Issue number16
StatePublished - 24 Apr 2024


FundersFunder number
Israel‐United States Science Foundation
Yoran Institute for Human Genome Research
Bloom's Syndrome Foundation2019049
Bloom's Syndrome Foundation
Tel Aviv University


    • MT2A
    • NO synthase (NOS)
    • autism spectrum disorder (ASD)
    • metallothionein
    • mitochondrial dysfunction
    • nitric oxide (NO)
    • tetrahydrobiopterin


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