ArticleNature medicine2014
CAPON-nNOS coupling can serve as a target for developing new anxiolytics.
Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 101 citations in OpenAlex.
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- Screening potential diagnostic biomarkers for PLA2R‑associated idiopathic membranous nephropathy by WGCNA analysis and LASSO algorithm.Renal failure · 2025Article
- Recessive variants in the intergenic NOS1AP-C1orf226 locus cause monogenic kidney disease responsive to anti-proteinuric treatment.Nature communications · 2025Article
- Electroacupuncture attenuates anxiety caused by chronic mild stress through inhibiting NOX2-derived oxidative stress in ventral hippocampus.Neurobiology of stress · 2025Article
- DjCapon Affects the Neural Regeneration and Light Sensitivity via NO and Wnt5a Signaling in Planarian Dugesia japonica.Molecular neurobiology · 2025Article
- FromActa pharmaceutica Sinica. B · 2025Article
- Targeting CAPON to modulate the CAPON-NOS Axis: a computational approach.Computational and structural biotechnology journal · 2025Article
- Disrupting stroke-induced GAT-1-syntaxin1A interaction promotes functional recovery after stroke.Cell reports. Medicine · 2024Article
- Rasd1 is involved in white matter injury through neuron-oligodendrocyte communication after subarachnoid hemorrhage.CNS neuroscience & therapeutics · 2024Article
- nNOS in Erbb4-positive neurons regulates GABAergic transmission in mouse hippocampus.Cell death & disease · 2024Article
- Preclinical evaluation of ZL006-05, a new antistroke drug with fast-onset antidepressant and anxiolytic effects.Stroke and vascular neurology · 2023Article
- "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
- Hippocampus: Molecular, Cellular, and Circuit Features in Anxiety.Neuroscience bulletin · 2023Review
- Enhanced AMPAR-dependent synaptic transmission by S-nitrosylation in the vmPFC contributes to chronic inflammatory pain-induced persistent anxiety in mice.Acta pharmacologica Sinica · 2023Article
- Targeting NMDA Receptors at the Neurovascular Unit: Past and Future Treatments for Central Nervous System Diseases.International journal of molecular sciences · 2022Review
- Ras Inhibitor Lonafarnib Rescues Structural and Functional Impairments of Synapses of AβThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Ion flux-independent NMDA receptor signaling.Neuropharmacology · 2022Review
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anxiety disorders are highly prevalent psychiatric diseases. There is need for a deeper understanding of anxiety control mechanisms in the mammalian brain and for development of new anxiolytic agents. Here we report that the coupling between neuronal nitric oxide synthase (nNOS) and its carboxy-terminal PDZ ligand (CAPON) can serve as a target for developing new anxiolytic agents. Augmenting nNOS-CAPON interaction in the hippocampus of mice by overexpressing full-length CAPON gave rise to anxiogenic-like behaviors, whereas dissociating CAPON from nNOS by overexpressing CAPON-125C or CAPON-20C (the C-terminal 125 or 20 amino acids of CAPON) or delivering Tat-CAPON-12C (a peptide comprising Tat and the 12 C-terminal amino acids of CAPON) in the hippocampus of mice produced anxiolytic-like effects. Mice subjected to chronic mild stress (CMS) displayed a substantial increase in nNOS-CAPON coupling in the hippocampus and a consequent anxiogenic-like phenotype. Disrupting nNOS-CAPON coupling reversed the CMS-induced anxiogenic-like behaviors. Moreover, small-molecule blockers of nNOS-CAPON binding rapidly produced anxiolytic-like effects. Dexamethasone-induced ras protein 1 (Dexras1)-extracellular signal-regulated kinase (ERK) signaling was involved in the behavioral effects of nNOS-CAPON association. Thus, nNOS-CAPON association contributes to the modulation of anxiety-related behaviors via regulating Dexras1-ERK signaling and can serve as a target for developing potential anxiolytics.
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Registered trials
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.