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CAPON-nNOS coupling can serve as a target for developing new anxiolytics
Li-Juan Zhu1, Ting-You Li2, Chun-Xia Luo3
11] Laboratory of Cerebrovascular Disease, Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing Medical University, Nanjing, China. [2] Department of Pharmacology, Nanjing Medical University, Nanjing, China. [3].
Targeting the interaction between neuronal nitric oxide synthase (nNOS) and CAPON in the hippocampus shows promise for developing new anxiety treatments. Disrupting this nNOS-CAPON coupling reduces anxiety-like behaviors, offering a novel therapeutic avenue.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- Anxiety disorders are common and require better understanding of brain mechanisms.
- Novel anxiolytic agents are needed to address these prevalent conditions.
Purpose of the Study:
- To investigate the role of neuronal nitric oxide synthase (nNOS)-CAPON coupling in anxiety.
- To explore nNOS-CAPON interaction as a potential target for anxiolytic drug development.
Main Methods:
- Mice models were used to manipulate nNOS-CAPON interaction via gene overexpression and peptide delivery in the hippocampus.
- Chronic mild stress (CMS) was employed to induce anxiety-like behaviors.
- Small-molecule blockers of nNOS-CAPON binding were tested.
- The involvement of Dexras1-ERK signaling was examined.
Main Results:
- Augmenting nNOS-CAPON interaction increased anxiety-like behaviors.
- Dissociating CAPON from nNOS or disrupting the coupling reduced anxiety-like behaviors.
- CMS increased nNOS-CAPON coupling and anxiety, which was reversed by disrupting the interaction.
- Small-molecule blockers of nNOS-CAPON binding showed rapid anxiolytic effects.
- Dexras1-ERK signaling was implicated in the observed behavioral effects.
Conclusions:
- nNOS-CAPON association is a key modulator of anxiety-related behaviors in the hippocampus.
- The nNOS-CAPON pathway, via Dexras1-ERK signaling, represents a viable target for developing novel anxiolytic therapies.
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