ArticleMolecular neurobiology2016
nNOS Translocates into the Nucleus and Interacts with Sox2 to Protect Neurons Against Early Excitotoxicity via Promotion of Shh Transcription.
Article in Molecular neurobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- NSUN4-mediated m5C RNA methylation protects retinal cells against excitotoxic injury via the SHH signaling pathway.PloS one · 2026Article
- Molecular mechanisms of excitotoxicity and their relevance to the pathogenesis of neurodegenerative diseases-an update.Acta pharmacologica Sinica · 2025Review
- Ischemic stroke and intervention strategies based on the timeline of stroke progression: Review and prospects.Acta pharmaceutica Sinica. B · 2025Review
- Characterization of Sonic Hedgehog transcripts in the adult mouse brain: co-expression with neuronal and oligodendroglial markers.Brain structure & function · 2024Article
- Sonic Hedgehog Signaling Pathway: A Role in Pain Processing.Neurochemical research · 2023Review
- Prophylactic Activation of Shh Signaling Attenuates TBI-Induced Seizures in Zebrafish by Modulating Glutamate Excitotoxicity through Eaat2a.Biomedicines · 2021Article
- Depleting SOX2 improves ischemic stroke via lncRNA PVT1/microRNA-24-3p/STAT3 axis.Molecular medicine (Cambridge, Mass.) · 2021Article
- The Role of Sonic Hedgehog Pathway in the Development of the Central Nervous System and Aging-Related Neurodegenerative Diseases.Frontiers in molecular biosciences · 2021Review
- Mitochondrial Protection and Against Glutamate Neurotoxicity via Shh/Ptch1 Signaling Pathway to Ameliorate Cognitive Dysfunction by Kaixin San in Multi-Infarct Dementia Rats.Oxidative medicine and cellular longevity · 2021Article
- RETRACTION: The Major Heat Shock Proteins, Hsp70 and Hsp90, in 2-Methoxyestradiol-Mediated Osteosarcoma Cell Death Model.International journal of molecular sciences · 2020Article
- Systematical Identification of the Protective Effect of Danhong Injection and BuChang NaoXinTong Capsules on Transcription Factors in Cerebral Ischemia Mice Brain.Oxidative medicine and cellular longevity · 2020Article
- Toxic Effects of 3,3'-Iminodipropionitrile on Vestibular System in Adult C57BL/6J MiceNeural plasticity · 2020Article
- The Neuroprotective Roles of Sonic Hedgehog Signaling Pathway in Ischemic Stroke.Neurochemical research · 2018Review
- Focal, but not global, cerebral ischaemia causes loss of myenteric neurons and upregulation of vasoactive intestinal peptide in mouse ileum.International journal of experimental pathology · 2018Article
- O-GlcNAc Glycosylation of nNOS Promotes Neuronal Apoptosis Following Glutamate Excitotoxicity.Cellular and molecular neurobiology · 2017Article
- Sonic hedgehog signalling mediates astrocyte crosstalk with neurons to confer neuroprotection.Journal of neurochemistry · 2017Article
- The Expression of NP847 and Sox2 after TBI and Its Influence on NSCs.Frontiers in cellular neuroscience · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cerebral ischemic stroke is a major public health problem leading to high mortality rates and disability in adults. The NMDA receptor (NMDAR)/neuronal nitric oxide synthase (nNOS)/NO-dependent excitotoxicity has been recognized to play an important role in cerebral ischemic stroke pathogenesis. Accumulating evidence suggests that the biological function of nNOS is associated with its ability to couple proteins and its subcellular localization. Previously, we and others determined that nNOS could translocate into the nucleus in cultured astrocytes, but the underlying mechanisms and biological significance remained unclear. In the present study, we identified a specific interaction between nNOS and Sox2 (SRY (sex determining region Y)-box 2), a member of the Sox family of transcription factors, both in vivo and in vitro. Our studies showed that nNOS is transported into the nucleus and interacted with Sox2 to form a nNOS-Sox2 complex in neurons at the early stage following glutamate stimulation. Mechanistically, via activating the transcription of Shh (Sonic hedgehog), the downstream target of Sox2, this nNOS-Sox2 complex exerted a neuroprotective function against glutamate-induced excitotoxicity. Utilizing the MCAO focal ischemia model on rats, we further verified that the 'nNOS-Sox2-Shh' axis was involved in the ischemic neuronal injury. Taken together, our studies revealed that the 'nNOS-Sox2-Shh' axis functions as a novel feedback compensatory mechanism to protect neurons against the early excitotoxicity and ischemic injury.
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