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The NO Answer for Autism Spectrum Disorder

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 oxid...

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Autores principales: Tripathi, Manish Kumar, Ojha, Shashank Kumar, Kartawy, Maryam, Hamoudi, Wajeha, Choudhary, Ashwani, Stern, Shani, Aran, Adi, Amal, Haitham
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10401098/
https://www.ncbi.nlm.nih.gov/pubmed/37212048
http://dx.doi.org/10.1002/advs.202205783
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author Tripathi, Manish Kumar
Ojha, Shashank Kumar
Kartawy, Maryam
Hamoudi, Wajeha
Choudhary, Ashwani
Stern, Shani
Aran, Adi
Amal, Haitham
author_facet Tripathi, Manish Kumar
Ojha, Shashank Kumar
Kartawy, Maryam
Hamoudi, Wajeha
Choudhary, Ashwani
Stern, Shani
Aran, Adi
Amal, Haitham
author_sort Tripathi, Manish Kumar
collection PubMed
description 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.
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spelling pubmed-104010982023-08-05 The NO Answer for Autism Spectrum Disorder Tripathi, Manish Kumar Ojha, Shashank Kumar Kartawy, Maryam Hamoudi, Wajeha Choudhary, Ashwani Stern, Shani Aran, Adi Amal, Haitham Adv Sci (Weinh) Research Article 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. John Wiley and Sons Inc. 2023-05-22 /pmc/articles/PMC10401098/ /pubmed/37212048 http://dx.doi.org/10.1002/advs.202205783 Text en © 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Tripathi, Manish Kumar
Ojha, Shashank Kumar
Kartawy, Maryam
Hamoudi, Wajeha
Choudhary, Ashwani
Stern, Shani
Aran, Adi
Amal, Haitham
The NO Answer for Autism Spectrum Disorder
title The NO Answer for Autism Spectrum Disorder
title_full The NO Answer for Autism Spectrum Disorder
title_fullStr The NO Answer for Autism Spectrum Disorder
title_full_unstemmed The NO Answer for Autism Spectrum Disorder
title_short The NO Answer for Autism Spectrum Disorder
title_sort no answer for autism spectrum disorder
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10401098/
https://www.ncbi.nlm.nih.gov/pubmed/37212048
http://dx.doi.org/10.1002/advs.202205783
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