ArticleTranslational psychiatry2018
PSD95 and nNOS interaction as a novel molecular target to modulate conditioned fear: relevance to PTSD.
Article in Translational psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- Stigmasterol Is Associated with Alterations in nNOS-PSD95/CAPON Signaling and Synaptic Plasticity in a PTSD Model.Antioxidants (Basel, Switzerland) · 2026Article
- Neurobiological Correlates of Coping Strategies in PTSD: The Role of IGF-1, CASP-9, nNOS, and IL-10 Based on Brief-COPE Assessment.Current issues in molecular biology · 2025Article
- Nitrergic Signaling Mediation of Neurobehavioral Responses to Stress in Zebrafish.Journal of neurochemistry · 2025Review
- The regulation and mechanism of the cAMP-PKA pathway on PTSD-like behaviors exacerbated by alcohol exposure.Frontiers in pharmacology · 2025Article
- Mechanisms of Transsynaptic Degeneration in the Aging Brain.Aging and disease · 2024Review
- Molecular mechanisms underlying sex and treatment-dependent differences in an animal model of cue-exposure therapy for cocaine relapse prevention.Frontiers in neuroscience · 2024Article
- "NO" Time in Fear Response: Possible Implication of Nitric-Oxide-Related Mechanisms in PTSD.Molecules (Basel, Switzerland) · 2023Review
- nNOS and Neurological, Neuropsychiatric Disorders: A 20-Year Story.Neuroscience bulletin · 2023Review
- Novel Pharmacological Targets of Post-Traumatic Stress Disorders.Life (Basel, Switzerland) · 2023Review
- GluN2B-containing NMDARs in the mammalian brain: pharmacology, physiology, and pathology.Frontiers in molecular neuroscience · 2023Review
- Targeting neuronal nitric oxide synthase and the nitrergic system in post-traumatic stress disorder.Psychopharmacology · 2022Review
- Inhibition of PSD95-nNOS protein-protein interactions decreases morphine reward and relapse vulnerability in rats.Addiction biology · 2022Article
- Targeting PSD95/nNOS by ZL006 alleviates social isolation-induced heightened attack behavior in mice.Psychopharmacology · 2022Article
- Activation of α7 nicotinic acetylcholine receptor ameliorates HIV-associated neurology and neuropathology.Brain : a journal of neurology · 2021Article
- nNOS-mediated protein-protein interactions: promising targets for treating neurological and neuropsychiatric disorders.Journal of biomedical research · 2020Article
- Nitric oxide signalling in the brain and its control of bodily functions.British journal of pharmacology · 2020Review
- Neuroprotective effects of ZL006 in AβNeural regeneration research · 2020Article
- Association Between PSD95 Gene 3'UTR Single Nucleotide Polymorphism and Risk of Acute Ischemic Stroke in Chinese Han Population.Journal of molecular neuroscience : MN · 2020Article
- Disrupting nNOS-PSD95 Interaction Improves Neurological and Cognitive Recoveries after Traumatic Brain Injury.Cerebral cortex (New York, N.Y. : 1991) · 2020Article
- The small molecule GAT1508 activates brain-specific GIRK1/2 channel heteromers and facilitates conditioned fear extinction in rodents.The Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Stimulation of N-methyl-D-aspartic acid receptors (NMDARs) and the resulting increase of nitric oxide (NO) production are critical for fear memory formation. Following NMDAR activation, efficient production of NO requires linking the 95 kDa postsynaptic density protein (PSD95), a scaffolding protein to neuronal nitric oxide synthase (nNOS). A variety of previously studied NMDAR antagonists and NOS inhibitors can disrupt fear conditioning, but they also affect many other CNS functions such as motor activity, anxiety, and learning. We hypothesized that disrupting nNOS and PSD95 interaction in the amygdala, a critical site for fear memory formation, will reduce conditioned fear. Our results show that systemic treatment with ZL006, a compound that disrupts PSD95/nNOS binding, attenuates fear memory compared to its inactive isomer ZL007. Co-immunoprecipitation after fear conditioning showed a robust increase in the amygdala PSD95/nNOS binding, which was blocked by systemic pre-administration of ZL006. Treatment of amygdala slices with ZL006 also impaired long-term potentiation (LTP), a cellular signature of synaptic plasticity. Direct intra-amygdala infusion of ZL006 also attenuated conditioned fear. Finally, unlike NMDAR antagonist MK-801, ZL006 does not affect locomotion, social interaction, object recognition memory, and spatial memory. These findings support the hypothesis that disrupting the PSD95/nNOS interaction downstream of NMDARs selectively reduces fear memory, and highlights PSD95/nNOS interaction as a novel target for fear-related disorders, such as posttraumatic stress disorder.
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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.