ArticleInternational journal of molecular sciences2021
Sigma-1 Receptor (S1R) Interaction with Cholesterol: Mechanisms of S1R Activation and Its Role in Neurodegenerative Diseases.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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.
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Who cites it
31 citing papers in PubMed, 42 citations in OpenAlex.
- Blarcamesine for the treatment of Early Alzheimer's Disease: Results from the ANAVEX2-73-AD-004 Phase IIB/III trial.The journal of prevention of Alzheimer's disease · 2025Trial
- Inter-Organelle Membrane Contact Sites as Physiological Regulatory Hubs in the Brain: From Neurons to Glial Cells.Biomolecules · 2026Review
- MD Simulations of Human Sigma-1 Receptor Trimer Uncover Cholesterol-Dependent Stabilization and Ligand-Specific Dynamics.Journal of chemical information and modeling · 2026Article
- Article
- Pridopidine Protects ALS Patient-Derived Neural Progenitor Cells via Sigma-1 Receptor Activation.International journal of molecular sciences · 2026Article
- Sigma-1 receptor regulates HIV-1 and methamphetamine-induced endothelial/pericyte barrier impairment via strain-specific inflammatory responses and mitochondrial dysregulation.Journal of neuroinflammation · 2026Article
- The lipid-modulating effect of berberine in hyperlipidemic ApoE-/- mice.Frontiers in pharmacology · 2026Article
- Pridopidine, a Potent and Selective Therapeutic Sigma-1 Receptor (S1R) Agonist for Treating Neurodegenerative Diseases.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Sigma-1 Receptor Ligands for CNS Cancer Treatment.CNS drugs · 2025Review
- Choline-An Essential Nutrient with Health Benefits and a Signaling Molecule.International journal of molecular sciences · 2025Review
- Sigma-1 Receptor Specific Biological Functions, Protective Role, and Therapeutic Potential in Cardiovascular Diseases.Cardiovascular toxicology · 2025Review
- Sigma 1 Receptor and Its Pivotal Role in Neurological Disorders.ACS pharmacology & translational science · 2025Review
- Berberine modulates cardiovascular diseases as a multitarget-mediated alkaloid with insights into its downstream signals usingSaudi journal of biological sciences · 2024Article
- 10th European Calcium Society symposium: The Ca2+-signaling toolkit in cell function, health and disease.Biology open · 2024Review
- 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
- Mitochondria-associated membrane collapse impairs TBK1-mediated proteostatic stress response in ALS.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Structure-Based Modeling of Sigma 1 Receptor Interactions with Ligands and Cholesterol and Implications for Its Biological Function.International journal of molecular sciences · 2023Article
- Targeting Sigma Receptors for the Treatment of Neurodegenerative and Neurodevelopmental Disorders.CNS drugs · 2023Review
- SIGMAR1 Confers Innate Resilience against Neurodegeneration.International journal of molecular sciences · 2023Review
- Sphingoid Bases Regulate the Sigma-1 Receptor-Sphingosine andInternational journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
The sigma-1 receptor (S1R) is a 223 amino acid-long transmembrane endoplasmic reticulum (ER) protein. The S1R modulates the activity of multiple effector proteins, but its signaling functions are poorly understood. S1R is associated with cholesterol, and in our recent studies we demonstrated that S1R association with cholesterol induces the formation of S1R clusters. We propose that these S1R-cholesterol interactions enable the formation of cholesterol-enriched microdomains in the ER membrane. We hypothesize that a number of secreted and signaling proteins are recruited and retained in these microdomains. This hypothesis is consistent with the results of an unbiased screen for S1R-interacting partners, which we performed using the engineered ascorbate peroxidase 2 (APEX2) technology. We further propose that S1R agonists enable the disassembly of these cholesterol-enriched microdomains and the release of accumulated proteins such as ion channels, signaling receptors, and trophic factors from the ER. This hypothesis may explain the pleotropic signaling functions of the S1R, consistent with previously observed effects of S1R agonists in various experimental systems.
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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.