ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
The nNOS-p38MAPK pathway is mediated by NOS1AP during neuronal death.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.
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Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Cationic Arginine-Rich Peptides (CARPs): A Novel Class of Neuroprotective Agents With a Multimodal Mechanism of Action.Frontiers in neurology · 2020Pooled it
- Ischemic stroke and intervention strategies based on the timeline of stroke progression: Review and prospects.Acta pharmaceutica Sinica. B · 2025Review
- Poly-GR repeats associated with ALS/FTD geneScience signaling · 2024Article
- Two Signaling Modes Are Better than One: Flux-Independent Signaling by Ionotropic Glutamate Receptors Is Coming of Age.Biomedicines · 2024Review
- "NO" Time in Fear Response: Possible Implication of Nitric-Oxide-Related Mechanisms in PTSD.Molecules (Basel, Switzerland) · 2023Review
- The Physiological Function of nNOS-Associated CAPON Proteins and the Roles of CAPON in Diseases.International journal of molecular sciences · 2023Review
- nNOS and Neurological, Neuropsychiatric Disorders: A 20-Year Story.Neuroscience bulletin · 2023Review
- Targeting NMDA Receptors at the Neurovascular Unit: Past and Future Treatments for Central Nervous System Diseases.International journal of molecular sciences · 2022Review
- Ion flux-independent NMDA receptor signaling.Neuropharmacology · 2022Review
- A Selective Histamine H4 Receptor Antagonist, JNJ7777120, Role on glutamate Transporter Activity in Chronic Depression.Journal of personalized medicine · 2022Article
- NOS1AP is a novel molecular target and critical factor in TDP-43 pathology.Brain communications · 2022Article
- Recent Advances in the Modeling of Alzheimer's Disease.Frontiers in neuroscience · 2022Review
- NMDARs mediate peripheral and central sensitization contributing to chronic orofacial pain.Frontiers in cellular neuroscience · 2022Review
- Treatment of Cerebral Ischemia Through NMDA Receptors: Metabotropic Signaling and Future Directions.Frontiers in pharmacology · 2022Review
- Non-ionotropic NMDA receptor signaling gates bidirectional structural plasticity of dendritic spines.Cell reports · 2021Article
- nNOS-mediated protein-protein interactions: promising targets for treating neurological and neuropsychiatric disorders.Journal of biomedical research · 2020Article
- Effects of agmatine, glutamate, arginine, and nitric oxide on executive functions in children with attention deficit hyperactivity disorder.Journal of neural transmission (Vienna, Austria : 1996) · 2020Article
- Resonance energy transfer sensitises and monitors in situ switching of LOV2-based optogenetic actuators.Nature communications · 2020Article
- Molecular Mechanisms of Non-ionotropic NMDA Receptor Signaling in Dendritic Spine Shrinkage.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Functions of p38 MAP Kinases in the Central Nervous System.Frontiers in molecular neuroscience · 2020Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuronal nitric oxide synthase (nNOS) and p38MAPK are strongly implicated in excitotoxicity, a mechanism common to many neurodegenerative conditions, but the intermediary mechanism is unclear. NOS1AP is encoded by a gene recently associated with sudden cardiac death, diabetes-associated complications, and schizophrenia (Arking et al., 2006; Becker et al., 2008; Brzustowicz, 2008; Lehtinen et al., 2008). Here we find it interacts with p38MAPK-activating kinase MKK3. Excitotoxic stimulus induces recruitment of NOS1AP to nNOS in rat cortical neuron culture. Excitotoxic activation of p38MAPK and subsequent neuronal death are reduced by competing with the nNOS:NOS1AP interaction and by knockdown with NOS1AP-targeting siRNAs. We designed a cell-permeable peptide that competes for the unique PDZ domain of nNOS that interacts with NOS1AP. This peptide inhibits NMDA-induced recruitment of NOS1AP to nNOS and in vivo in rat, doubles surviving tissue in a severe model of neonatal hypoxia-ischemia, a major cause of neonatal death and pediatric disability. The highly unusual sequence specificity of the nNOS:NOS1AP interaction and involvement in excitotoxic signaling may provide future opportunities for generation of neuroprotectants with high specificity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.