The NO Answer for Autism Spectrum Disorder

Manish Kumar Tripathi, Shashank Kumar Ojha, Maryam Kartawy, Wajeha Hamoudi, Ashwani Choudhary, Shani Stern, Adi Aran, Haitham Amal*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Autism spectrum disorders (ASDs) include a wide range of neurodevelopmental disorders. Several reports showed that mutations in different high-risk ASD genes lead to ASD. However, the underlying molecular mechanisms have not been deciphered. Recently, they reported a dramatic increase in nitric oxide (NO) levels in ASD mouse models. Here, they conducted a multidisciplinary study to investigate the role of NO in ASD. High levels of nitrosative stress biomarkers are found in both the Shank3 and Cntnap2 ASD mouse models. Pharmacological intervention with a neuronal NO synthase (nNOS) inhibitor in both models led to a reversal of the molecular, synaptic, and behavioral ASD-associated phenotypes. Importantly, treating iPSC-derived cortical neurons from patients with SHANK3 mutation with the nNOS inhibitor showed similar therapeutic effects. Clinically, they found a significant increase in nitrosative stress biomarkers in the plasma of low-functioning ASD patients. Bioinformatics of the SNO-proteome revealed that the complement system is enriched in ASD. This novel work reveals, for the first time, that NO plays a significant role in ASD. Their important findings will open novel directions to examine NO in diverse mutations on the spectrum as well as in other neurodevelopmental disorders. Finally, it suggests a novel strategy for effectively treating ASD.

Original languageAmerican English
Article number2205783
JournalAdvanced Science
Volume10
Issue number22
DOIs
StatePublished - 4 Aug 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.

Keywords

  • S-nitrosylation
  • Shank3
  • autism spectrum disorder
  • behavior
  • contactin-associated protein-like2
  • nitric oxide

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