ReviewCurrent neuropharmacology2018
The Role of Sigma-1 Receptor, an Intracellular Chaperone in Neurodegenerative Diseases.
Review in Current neuropharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
84 citing papers in PubMed, 2 syntheses or guidelines pooled it, 124 citations in OpenAlex.
- Sigma-1 Receptor Ligand Blarcamesine (ANAVEX 2-73) for Alzheimer's Disease: A Systematic Review.CNS drugs · 2026Pooled it
- A neuroprotective target in the shadows: a scoping review of pharmacological gaps in σ1R agonists for glutamate-induced neurotoxicity.Frontiers in pharmacology · 2026Pooled it
- Safety, Pharmacokinetics, and Pharmacodynamics of a 6-h N,N-Dimethyltryptamine (DMT) Infusion in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Trial.Clinical and translational science · 2025Trial
- Sigma-1 Expression in Chronic Mouse Models of Temporal Lobe Epilepsy.Molecular neurobiology · 2026Article
- Neuromodulatory roles of the sigma-1 receptor in behavior and drug sensitization during development.Acta pharmacologica Sinica · 2026Article
- Effects of fenfluramine and sigma-1-dependent pharmacological and genetic modulation in a mouse kindling model.Epilepsia · 2026Article
- Targeting endoplasmic reticulum stress and protein misfolding in schizophrenia: the emerging promise of sigma-1 receptor agonists.Psychopharmacology · 2026Review
- The Role of Sigmar1 in Autophagy Regulation and Disease Therapy.International journal of molecular sciences · 2026Review
- Targeting Sigma-1 and Sigma-2 Receptors in Neuropathic Pain: Pharmacology, Ligand Development, and Translational Progress.Brain sciences · 2026Review
- Enhanced mitochondria-associated membrane formation in Fuchs endothelial corneal dystrophy: a novel link between endoplasmic reticulum stress and mitochondrial dysfunction.Japanese journal of ophthalmology · 2026Article
- Sigma-1 and Sigma-2 receptors exhibit divergent genome-wide Co-expression architectures in human brain despite shared subcellular localization.Frontiers in pharmacology · 2026Article
- The lipid-modulating effect of berberine in hyperlipidemic ApoE-/- mice.Frontiers in pharmacology · 2026Article
- Heavy alcohol consumption attenuates human mesenteric artery responsiveness to sigma receptor-1 ligands.American journal of physiology. Heart and circulatory physiology · 2026Article
- Article
- Astrocyte Autophagy in Neurodegenerative Diseases: Current Progress in Mechanisms and Therapeutics.Neurochemical research · 2025Review
- Dynamic expression of the myocardial sigma-1 receptor after doxorubicin cardiomyopathy using radioiodine-labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5 V) imaging.Annals of nuclear medicine · 2025Article
- Voltage-Gated Sodium Channel Dysfunction in Epilepsy: Zebrafish Models for Therapeutics.Biomedicines · 2025Review
- Neurosteroids, Microbiota, and Neuroinflammation: Mechanistic Insights and Therapeutic Perspectives.International journal of molecular sciences · 2025Review
- Sigma‑2 Receptor/Transmembrane Protein 97 in Pain Modulation: Tracing Historical Roots and Current Research Directions.ACS pharmacology & translational science · 2025Review
- Targeting the sigma-1 receptor with pridopidine induces functional neurorestoration in spinal cord ischemia-reperfusion injury.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWidespread protein aggregation occurs in the living system under stress or during aging, owing to disturbance of endoplasmic reticulum (ER) proteostasis. Many neurodegenerative diseases may have a common mechanism: the failure of protein homeostasis. Perturbation of ER results in unfolded protein response (UPR). Prolonged chronical UPR may activate apoptotic pathways and cause cell death.
methodsResearch articles on Sigma-1 receptor were reviewed.
resultsER is associated to mitochondria by the mitochondria-associated ER-membrane, MAM. The sigma-1 receptor (Sig-1R), a well-known ER-chaperone localizes in the MAM. It serves for Ca2+-signaling between the ER and mitochondria, involved in ion channel activities and especially important during neuronal differentiation. Sig-1R acts as central modulator in inter-organelle signaling. Sig-1R helps cell survival by attenuating ER-stress. According to sequence based predictions Sig-1R is a 223 amino acid protein with two transmembrane (2TM) domains. The X-ray structure of the Sig-1R [1] showed a membrane-bound trimeric assembly with one transmembrane (1TM) region. Despite the in vitro determined assembly, the results of in vivo studies are rather consistent with the 2TM structure. The receptor has unique and versatile pharmacological profile. Dimethyl tryptamine (DMT) and neuroactive steroids are endogenous ligands that activate Sig-1R. The receptor has a plethora of interacting client proteins. Sig-1R exists in oligomeric structures (dimer-trimer-octamer-multimer) and this fact may explain interaction with diverse proteins.
conclusionSig-1R agonists have been used in the treatment of different neurodegenerative diseases, e.g. Alzheimer's and Parkinson's diseases (AD and PD) and amyotrophic lateral sclerosis. Utilization of Sig-1R agents early in AD and similar other diseases has remained an overlooked therapeutic opportunity.
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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.