ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Neurabin scaffolding of adenosine receptor and RGS4 regulates anti-seizure effect of endogenous adenosine.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- SnRNA-seq reveals seizure-induced remodelling of excitatory and inhibitory neuron populations.Scientific reports · 2026Article
- Proteomic Characterization of Striatal Neurabin Interactome and Its Sex Specific Impact on Motor Behavior.ACS chemical neuroscience · 2026Article
- Proteomic Characterization of Striatal Neurabin Interactome and its Sex Specific Impact on Motor Behavior.bioRxiv : the preprint server for biology · 2025Article
- Purinergic Signalling in the Cochlea.International journal of molecular sciences · 2022Review
- A peptide blocking the ADORA1-neurabin interaction is anticonvulsant and inhibits epilepsy in an Alzheimer's model.JCI insight · 2022Article
- SIPA1L1/SPAR1 Interacts with the Neurabin Family of Proteins and is Involved in GPCR Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Synergistic regulation ofRNA biology · 2021Article
- Regulation of Synaptic Transmission and Plasticity by Protein Phosphatase 1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Review
- Regulator of G Protein Signalling 4 (RGS4) as a Novel Target for the Treatment of Sensorineural Hearing Loss.International journal of molecular sciences · 2020Article
- β-amyloid redirects norepinephrine signaling to activate the pathogenic GSK3β/tau cascade.Science translational medicine · 2020Article
- An Interhelical Salt Bridge Controls Flexibility and Inhibitor Potency for Regulators of G-protein Signaling Proteins 4, 8, and 19.Molecular pharmacology · 2019Article
- Purinergic Signaling and Cochlear Injury-Targeting the Immune System?International journal of molecular sciences · 2019Review
- Interplay of cysteine exposure and global protein dynamics in small-molecule recognition by a regulator of G-protein signaling protein.Proteins · 2019Article
- Distinct Roles of Protein Phosphatase 1 Bound on Neurabin and Spinophilin and Its Regulation in AMPA Receptor Trafficking and LTD Induction.Molecular neurobiology · 2018Article
- A High-Throughput Time-Resolved Fluorescence Energy Transfer Assay to Screen for Modulators of RGS7/Gβ5/R7BP Complex.Assay and drug development technologies · 2018Article
- Effective Attenuation of Adenosine A1R Signaling by Neurabin Requires Oligomerization of Neurabin.Molecular pharmacology · 2017Article
- The amyloid precursor protein modulates αFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Diverse arrestin-recruiting and endocytic profiles of tricyclic antipsychotics acting as direct αNeuropharmacology · 2017Article
- Age-dependent differential regulation of anxiety- and depression-related behaviors by neurabin and spinophilin.PloS one · 2017Article
- Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis).International journal of molecular medicine · 2015Review
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7 authors at 2 institutions in 1 country.
Funding
Abstract
Endogenous adenosine is an essential protective agent against neural damage by various insults to the brain. However, the therapeutic potential of adenosine receptor-directed ligands for neuroprotection is offset by side effects in peripheral tissues and organs. An increase in adenosine receptor responsiveness to endogenous adenosine would enhance neuroprotection while avoiding the confounding effects of exogenous ligands. Here we report novel regulation of adenosine-evoked responses by a neural tissue-specific protein, neurabin. Neurabin attenuated adenosine A(1) receptor (A1R) signaling by assembling a complex between the A1R and the regulator of G-protein signaling 4 (RGS4), a protein known to turn off G-protein signaling. Inactivation of the neurabin gene enhanced A1R signaling and promoted the protective effect of adenosine against excitotoxic seizure and neuronal death in mice. Furthermore, administration of a small molecule inhibitor of RGS4 significantly attenuated seizure severity in mice. Notably, the dose of kainate capable of inducing an ∼50% rate of death in wild-type (WT) mice did not affect neurabin-null mice or WT mice cotreated with an RGS4 inhibitor. The enhanced anti-seizure and neuroprotective effect achieved by disruption of the A1R/neurabin/RGS4 complex is elicited by the on-site and on-demand release of endogenous adenosine, and does not require administration of A1R ligands. These data identify neurabin-RGS4 as a novel tissue-selective regulatory mechanism for fine-tuning adenosine receptor function in the nervous system. Moreover, these findings implicate the A1R/neurabin/RGS4 complex as a valid therapeutic target for specifically manipulating the neuroprotective effects of endogenous adenosine.
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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.