The NO Answer for Autism Spectrum Disorder.
S-nitrosylation
Shank3
autism spectrum disorder
behavior
contactin-associated protein-like2
nitric oxide
Journal
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
revised:
19
04
2023
received:
07
10
2022
medline:
7
8
2023
pubmed:
22
5
2023
entrez:
22
5
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37212048
doi: 10.1002/advs.202205783
pmc: PMC10401098
doi:
Substances chimiques
Nitric Oxide
31C4KY9ESH
Biomarkers
0
Shank3 protein, mouse
0
Microfilament Proteins
0
Nerve Tissue Proteins
0
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2205783Subventions
Organisme : US Department of Defense (DoD)
Organisme : Israeli Science Foundation
Organisme : Eagles Autism Foundation
Organisme : National Institute of Psychobiology in Israel
Organisme : Israeli Council for Higher Education Maof Grant
Organisme : Berettler Centre for Research in Molecular Pharmacology and Therapeutics Grant
Organisme : Satell Family Foundation and the Neubauer Family Foundation
Informations de copyright
© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.
Références
Aging Cell. 2007 Jun;6(3):351-9
pubmed: 17388798
Mol Psychiatry. 2012 Jan;17(1):71-84
pubmed: 21606927
Neurosci Lett. 2007 Jun 21;421(1):72-6
pubmed: 17548163
Hum Mol Genet. 2018 Jun 1;27(11):1941-1954
pubmed: 29788201
Mol Autism. 2020 May 27;11(1):40
pubmed: 32460854
Redox Biol. 2021 May;41:101904
pubmed: 33706169
Free Radic Biol Med. 2022 Aug 1;188:83-91
pubmed: 35716826
Biochem Biophys Rep. 2021 Feb 01;25:100916
pubmed: 33553685
Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):1012-6
pubmed: 11792847
Braz J Med Biol Res. 2003 Feb;36(2):239-45
pubmed: 12563527
Curr Protoc Neurosci. 2011 Jul;Chapter 8:Unit 8.26
pubmed: 21732314
Proc Natl Acad Sci U S A. 2015 May 12;112(19):6176-81
pubmed: 25918374
Front Neurosci. 2020 Feb 05;14:23
pubmed: 32116493
J Cell Biol. 2003 Sep 15;162(6):1149-60
pubmed: 12963709
Nat Protoc. 2013 Dec;8(12):2531-7
pubmed: 24263092
Transl Psychiatry. 2022 Mar 28;12(1):127
pubmed: 35351881
Am J Hum Genet. 2007 Dec;81(6):1289-97
pubmed: 17999366
J Affect Disord. 2013 Dec;151(3):1041-52
pubmed: 24126118
Cell. 2013 Nov 21;155(5):1008-21
pubmed: 24267887
Brain Sci. 2020 May 20;10(5):
pubmed: 32443912
Indian J Psychiatry. 2013 Jul;55(3):220-3
pubmed: 24082241
Transl Psychiatry. 2021 Sep 17;11(1):480
pubmed: 34535637
Nucleic Acids Res. 2015 Jan;43(Database issue):D447-52
pubmed: 25352553
J Pharmacol Sci. 2015 Oct;129(2):119-26
pubmed: 26422672
J Neurochem. 1999 Aug;73(2):727-35
pubmed: 10428070
J Hum Genet. 2003;48(10):495-501
pubmed: 13680297
Mol Psychiatry. 2018 Mar;23(3):735-746
pubmed: 28948968
CNS Drugs. 2018 Aug;32(8):713-734
pubmed: 30105528
Mol Cell Neurosci. 2009 May;41(1):8-18
pubmed: 19386237
Nature. 2011 Apr 28;472(7344):437-42
pubmed: 21423165
Mol Psychiatry. 2003 Apr;8(4):407-12
pubmed: 12740598
Sci Rep. 2017 May 09;7:46041
pubmed: 28485374
Int J Neurosci. 2020 Oct;130(10):1047-1062
pubmed: 31914343
Biochim Biophys Acta Mol Cell Res. 2018 Nov;1865(11 Pt B):1718-1732
pubmed: 30992134
Mol Syndromol. 2012 Apr;2(3-5):186-201
pubmed: 22670140
Neuron. 2007 Jan 4;53(1):53-64
pubmed: 17196530
Cell. 2001 Sep 21;106(6):675-83
pubmed: 11572774
Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):4152-7
pubmed: 27035958
Semin Cell Dev Biol. 2022 May;125:84-90
pubmed: 34020876
Redox Biol. 2020 Jul;34:101567
pubmed: 32464501
Mol Autism. 2021 Jan 19;12(1):2
pubmed: 33468258
Biomedicines. 2020 May 15;8(5):
pubmed: 32429146
Neurobiol Dis. 2015 Dec;84:99-108
pubmed: 25796565
Autism Res. 2018 Jul;11(7):1076-1090
pubmed: 29761862
J Biol Chem. 2002 Mar 22;277(12):10273-82
pubmed: 11786535
J Neurodev Disord. 2021 Nov 16;13(1):55
pubmed: 34784886
Cell. 2016 Jan 14;164(1-2):170-182
pubmed: 26771490
J Biol Chem. 1994 Apr 29;269(17):12645-53
pubmed: 7513692
Neuron. 2013 Apr 10;78(1):8-27
pubmed: 23583105
J Mol Neurosci. 2021 Nov;71(11):2383-2392
pubmed: 33591546
Front Behav Neurosci. 2009 Jul 20;3:11
pubmed: 19649166
Cell Mol Life Sci. 2015 Jan;72(1):101-19
pubmed: 25213356
Dev Neurobiol. 2017 Apr;77(4):393-404
pubmed: 27390186
Transl Psychiatry. 2023 Jul 6;13(1):246
pubmed: 37414777
MMWR Surveill Summ. 2018 Nov 16;65(13):1-23
pubmed: 30439868
eNeuro. 2021 Oct 21;8(5):
pubmed: 34593517
Prog Brain Res. 2018;241:63-112
pubmed: 30447757
Brain Sci. 2021 May 21;11(6):
pubmed: 34064215
PLoS One. 2015 May 07;10(5):e0125633
pubmed: 25951243
Nat Commun. 2017 May 02;8:15096
pubmed: 28462915
Front Mol Neurosci. 2017 Feb 14;10:26
pubmed: 28261056
Ann Med. 1995 Jun;27(3):379-88
pubmed: 7546628
Dialogues Clin Neurosci. 2012 Sep;14(3):281-92
pubmed: 23226953
Front Aging Neurosci. 2021 Aug 24;13:717263
pubmed: 34504419
Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16958-63
pubmed: 20837516
Mass Spectrom Rev. 2015 Jul-Aug;34(4):423-48
pubmed: 24318073
Eur J Hum Genet. 2014 Feb;22(2):171-8
pubmed: 23714751
Pediatrics. 2004 May;113(5):e472-86
pubmed: 15121991
Philos Trans R Soc Lond B Biol Sci. 2013 Dec 02;369(1633):20130143
pubmed: 24298145
J Neurochem. 2000 Sep;75(3):991-1003
pubmed: 10936180
Neuron. 2016 Jan 6;89(1):147-62
pubmed: 26687841
Am J Hematol. 2009 Apr;84(4):221-7
pubmed: 19229985
Stem Cell Res. 2022 Oct;64:102899
pubmed: 36044808
Nat Rev Neurosci. 2021 Nov;22(11):657-673
pubmed: 34545240
Sci Rep. 2020 Aug 17;10(1):13913
pubmed: 32807865
Oxid Med Cell Longev. 2016;2016:9782346
pubmed: 26798429
Neurobiol Dis. 2020 Nov;145:105064
pubmed: 32889171
eNeuro. 2018 Oct 5;5(3):
pubmed: 30302388
Sci Adv. 2022 Dec 14;8(50):eade0764
pubmed: 36516243
Adv Sci (Weinh). 2023 Aug;10(22):e2205783
pubmed: 37212048
Pharmacol Ther. 2018 Oct;190:91-104
pubmed: 29763648
Neuroscience. 2018 Aug 1;384:41-53
pubmed: 29782905
PLoS One. 2012;7(10):e46995
pubmed: 23115634
J Leukoc Biol. 2011 Jun;89(6):873-91
pubmed: 21233414
Mol Psychiatry. 2021 Jun;26(6):1945-1966
pubmed: 32161363
Brain Struct Funct. 2017 Jan;222(1):1-20
pubmed: 27033097
Mol Neuropsychiatry. 2017 Jul;3(1):19-27
pubmed: 28879198
J Neurosci. 2015 Jul 1;35(26):9648-65
pubmed: 26134648
Cell. 2011 Sep 30;147(1):235-46
pubmed: 21962519
Nature. 2009 Dec 17;462(7275):920-4
pubmed: 19946265
Nature. 2011 May 12;473(7346):221-5
pubmed: 21490598
Alcohol Alcohol. 2001 May-Jun;36(3):193-8
pubmed: 11373254
Int J Mol Sci. 2020 May 31;21(11):
pubmed: 32486366
Neurosci Lett. 2017 Jul 13;653:283-287
pubmed: 28579483
Neurotherapeutics. 2015 Jul;12(3):620-30
pubmed: 25894671
Front Psychiatry. 2022 Mar 01;13:813304
pubmed: 35299821
Prog Brain Res. 1994;103:359-64
pubmed: 7886218
Mol Psychiatry. 2021 Dec;26(12):7498-7508
pubmed: 34535765
Eur J Hum Genet. 2013 Mar;21(3):310-6
pubmed: 22892527
Front Cell Neurosci. 2019 Aug 20;13:385
pubmed: 31481879
Mol Psychiatry. 2020 Aug;25(8):1835-1848
pubmed: 29988084
J Vis Exp. 2008 Dec 22;(22):
pubmed: 19229173
J Comp Neurol. 1989 Feb 8;280(2):197-212
pubmed: 2494237
Neurosci Lett. 2012 Jan 11;506(2):277-80
pubmed: 22133810
Cell Mol Neurobiol. 2010 Mar;30(2):161-71
pubmed: 19774457
Nat Commun. 2016 May 10;7:11459
pubmed: 27161151