ArticleProceedings of the National Academy of Sciences of the United States of America2015
Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 116 citations in OpenAlex.
- Sigma-1 Receptor Mitigates Poly-GR-Associated Redox Dysregulation by Restoring NRF2/HO1 Signaling in C9orf72-Associated ALS.Neuromolecular medicine · 2026Article
- Article
- Cocaine affects astrocyte iNOS expression.Brain research · 2026Article
- Pridopidine, a Potent and Selective Therapeutic Sigma-1 Receptor (S1R) Agonist for Treating Neurodegenerative Diseases.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Repurposing Sigma-1 Receptor-Targeting Drugs for Therapeutic Advances in Neurodegenerative Disorders.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Sigma 1 Receptor and Its Pivotal Role in Neurological Disorders.ACS pharmacology & translational science · 2025Review
- Advancing depression treatment: the role of sigma receptor ligands.Frontiers in neuroscience · 2025Review
- The sigma-1 receptor as a neurohomeostatic decision hub for GABARAP-mediated receptor trafficking and macroautophagy.Frontiers in molecular biosciences · 2025Article
- Epigenetic mechanisms of rapid-acting antidepressants.Translational psychiatry · 2024Review
- A single dose of cocaine rewires the 3D genome structure of midbrain dopamine neurons.bioRxiv : the preprint server for biology · 2024Article
- Transmembrane protein TMEM97 and epigenetic reader BAHCC1 constitute an axis that supports pro-inflammatory cytokine expression.Cellular signalling · 2024Article
- Sigma-1 receptor activation mediates the sustained antidepressant effect of ketamine in mice via increasing BDNF levels.Acta pharmacologica Sinica · 2024Article
- Benzomorphan and non-benzomorphan agonists differentially alter sigma-1 receptor quaternary structure, as does types of cellular stress.Cellular and molecular life sciences : CMLS · 2024Article
- T cell infiltration into the brain triggers pulmonary dysfunction in murine Cryptococcus-associated IRIS.Nature communications · 2023Article
- Sphingoid Bases Regulate the Sigma-1 Receptor-Sphingosine andInternational journal of molecular sciences · 2023Article
- Sigma-1 Receptor Signaling: In Search of New Therapeutic Alternatives for Cardiovascular and Renal Diseases.International journal of molecular sciences · 2023Review
- Overview of Sigma-1R Subcellular Specific Biological Functions and Role in Neuroprotection.International journal of molecular sciences · 2023Review
- Dopamine, Immunity, and Disease.Pharmacological reviews · 2023Review
- Defining the ligand-dependent proximatome of the sigma 1 receptor.Frontiers in cell and developmental biology · 2023Article
- Sigma-1 receptor agonist PRE-084 confers protection against TAR DNA-binding protein-43 toxicity through NRF2 signalling.Redox biology · 2022Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The sigma-1 receptor (Sig-1R) chaperone at the endoplasmic reticulum (ER) plays important roles in cellular regulation. Here we found a new function of Sig-1R, in that it translocates from the ER to the nuclear envelope (NE) to recruit chromatin-remodeling molecules and regulate the gene transcription thereof. Sig-1Rs mainly reside at the ER-mitochondrion interface. However, on stimulation by agonists such as cocaine, Sig-1Rs translocate from ER to the NE, where Sig-1Rs bind NE protein emerin and recruit chromatin-remodeling molecules, including lamin A/C, barrier-to-autointegration factor (BAF), and histone deacetylase (HDAC), to form a complex with the gene repressor specific protein 3 (Sp3). Knockdown of Sig-1Rs attenuates the complex formation. Cocaine was found to suppress the gene expression of monoamine oxidase B (MAOB) in the brain of wild-type but not Sig-1R knockout mouse. A single dose of cocaine (20 mg/kg) in rats suppresses the level of MAOB at nuclear accumbens without affecting the level of dopamine transporter. Daily injections of cocaine in rats caused behavioral sensitization. Withdrawal from cocaine in cocaine-sensitized rats induced an apparent time-dependent rebound of the MAOB protein level to about 200% over control on day 14 after withdrawal. Treatment of cocaine-withdrawn rats with the MAOB inhibitor deprenyl completely alleviated the behavioral sensitization to cocaine. Our results demonstrate a role of Sig-1R in transcriptional regulation and suggest cocaine may work through this newly discovered genomic action to achieve its addictive action. Results also suggest the MAOB inhibitor deprenyl as a therapeutic agent to block certain actions of cocaine during withdrawal.
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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.