ArticleThe Journal of clinical investigation2020
Functional α6β4 acetylcholine receptor expression enables pharmacological testing of nicotinic agonists with analgesic properties.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 18 citations in OpenAlex.
- Naltrexone, Naloxone, Morphine, and Fentanyl Pharmacologically Chaperone a Mutant μ-Opioid Receptor via an Endoplasmic Reticulum Exit Site-Dependent Pathway.Pharmacology research & perspectives · 2026Article
- Precision neuroscience.Nature biotechnology · 2025Article
- Molecular insights into the α6β4 nicotinic acetylcholine receptor function and ligand recognition.Nature communications · 2025Article
- Article
- "Unraveling the role ofReceptors (Basel, Switzerland) · 2025Article
- The Role of Alpha-7 Nicotinic Acetylcholine Receptors in Pain: Potential Therapeutic Implications.Current neuropharmacology · 2025Review
- A novel α-conotoxin [D1G, ΔQ14] LvIC decreased mouse locomotor activity.Frontiers in pharmacology · 2024Article
- Molecular Determinants of Species Specificity of α-Conotoxin TxIB towards Rat and Human α6/α3β4 Nicotinic Acetylcholine Receptors.International journal of molecular sciences · 2023Article
- Different efficiency of auxiliary/chaperone proteins to promote the functional reconstitution of honeybee glutamate and acetylcholine receptors in Xenopus laevis oocytes.Insect molecular biology · 2022Article
- Computational and Functional Mapping of Human and Rat α6β4 Nicotinic Acetylcholine Receptors Reveals Species-Specific Ligand-Binding Motifs.Journal of medicinal chemistry · 2021Article
- Proteins for increased surface expression of the α6β4 nicotinic acetylcholine receptor: nothing but good news?The Journal of clinical investigation · 2020Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The α6β4 nicotinic acetylcholine receptor (nAChR) is enriched in dorsal root ganglia neurons and is an attractive non-opioid therapeutic target for pain. However, difficulty expressing human α6β4 receptors in recombinant systems has precluded drug discovery. Here, genome-wide screening identified accessory proteins that enable reconstitution of human α6β4 nAChRs. BARP, an auxiliary subunit of voltage-dependent calcium channels, promoted α6β4 surface expression while IRE1α, an unfolded protein response sensor, enhanced α6β4 receptor assembly. Effects on α6β4 involve BARP's N-terminal region and IRE1α's splicing of XBP1 mRNA. Furthermore, clinical efficacy of nicotinic agents in relieving neuropathic pain best correlated with their activity on α6β4. Finally, BARP-knockout, but not NACHO-knockout mice lacked nicotine-induced antiallodynia, highlighting the functional importance of α6β4 in pain. These results identify roles for IRE1α and BARP in neurotransmitter receptor assembly and unlock drug discovery for the previously elusive α6β4 receptor.
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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.