Gene Symbol: SIGMAR1
Description: sigma non-opioid intracellular receptor 1
Alias: ALS16, DSMA2, OPRS1, SIG-1R, SR-BP, SR-BP1, SRBP, hSigmaR1, sigma1R, sigma non-opioid intracellular receptor 1, SR31747 binding protein 1, aging-associated gene 8 protein, sigma 1-type opioid receptor
Species: human
Products:     SIGMAR1

Top Publications

  1. Kekuda R, Prasad P, Fei Y, Leibach F, Ganapathy V. Cloning and functional expression of the human type 1 sigma receptor (hSigmaR1). Biochem Biophys Res Commun. 1996;229:553-8 pubmed
    ..The hSigmaR1 cDNA predicts a protein of 223 amino acids with a single putative transmembrane domain...
  2. Wu Z, Bowen W. Role of sigma-1 receptor C-terminal segment in inositol 1,4,5-trisphosphate receptor activation: constitutive enhancement of calcium signaling in MCF-7 tumor cells. J Biol Chem. 2008;283:28198-215 pubmed publisher
    ..These results suggest that sigma-1R overexpression drives sigma agonist-independent dissociation of ANK 220 from IP3R-3, resulting in activation. The C-terminal segment plays a key role in the interaction. ..
  3. Aydar E, Onganer P, Perrett R, Djamgoz M, Palmer C. The expression and functional characterization of sigma (sigma) 1 receptors in breast cancer cell lines. Cancer Lett. 2006;242:245-57 pubmed
    ..This data suggests sigma1 receptor plays a role in proliferation and adhesion of breast cancer cells. Therefore, it is likely to be a potential target for the diagnosis and therapy of breast cancer. ..
  4. Kinoshita M, Matsuoka Y, Suzuki T, Mirrielees J, Yang J. Sigma-1 receptor alters the kinetics of Kv1.3 voltage gated potassium channels but not the sensitivity to receptor ligands. Brain Res. 2012;1452:1-9 pubmed publisher
    Sigma1 receptors (Sigma1R) are intracellular chaperone proteins that bind psychotropic drugs and also clinically used drugs such as ketamine and haloperidol...
  5. Amer M, McKeown L, Tumova S, Liu R, Seymour V, Wilson L, et al. Inhibition of endothelial cell Ca²? entry and transient receptor potential channels by Sigma-1 receptor ligands. Br J Pharmacol. 2013;168:1445-55 pubmed publisher
    ..Chemical foundations for TRP channel inhibitors are suggested. ..
  6. Seth P, Ganapathy M, Conway S, Bridges C, Smith S, Casellas P, et al. Expression pattern of the type 1 sigma receptor in the brain and identity of critical anionic amino acid residues in the ligand-binding domain of the receptor. Biochim Biophys Acta. 2001;1540:59-67 pubmed
    The type 1 sigma receptor (sigmaR1) has been shown to participate in a variety of functions in the central nervous system...
  7. Johannessen M, Ramachandran S, Riemer L, Ramos Serrano A, Ruoho A, Jackson M. Voltage-gated sodium channel modulation by sigma-receptors in cardiac myocytes and heterologous systems. Am J Physiol Cell Physiol. 2009;296:C1049-57 pubmed publisher
    ..The modulation of Na(v)1.5 channels by sigma-receptors in the heart suggests an important pathway by which drugs can alter cardiac excitability and rhythmicity. ..
  8. Luty A, Kwok J, Dobson Stone C, Loy C, Coupland K, Karlstrom H, et al. Sigma nonopioid intracellular receptor 1 mutations cause frontotemporal lobar degeneration-motor neuron disease. Ann Neurol. 2010;68:639-49 pubmed publisher
    ..672*51G>T) in the 3'-untranslated region (UTR) of the Sigma nonopioid intracellular receptor 1 (SIGMAR1) gene in affected individuals from the FTLD-MND pedigree. The c...
  9. Al Saif A, Al Mohanna F, Bohlega S. A mutation in sigma-1 receptor causes juvenile amyotrophic lateral sclerosis. Ann Neurol. 2011;70:913-9 pubmed publisher
    ..3 containing 9 RefSeq genes. Sequencing the SIGMAR1 gene revealed a mutation affecting a highly conserved amino acid located in the transmembrane domain of the ..

More Information

Publications113 found, 100 shown here

  1. Hayashi T, Su T. Regulating ankyrin dynamics: Roles of sigma-1 receptors. Proc Natl Acad Sci U S A. 2001;98:491-6 pubmed
  2. Crottès D, Martial S, Rapetti Mauss R, Pisani D, Loriol C, Pellissier B, et al. Sig1R protein regulates hERG channel expression through a post-translational mechanism in leukemic cells. J Biol Chem. 2011;286:27947-58 pubmed publisher
    ..Altogether, these results demonstrate for the first time that Sig1R controls ion channel expression through the regulation of subunit trafficking activity. ..
  3. Wang L, Eldred J, Sidaway P, Sanderson J, Smith A, Bowater R, et al. Sigma 1 receptor stimulation protects against oxidative damage through suppression of the ER stress responses in the human lens. Mech Ageing Dev. 2012;133:665-74 pubmed publisher
  4. Wall Medrano A, de la Rosa L, Vázquez Flores A, Mercado Mercado G, González Arellanes R, López Díaz J, et al. Lipidomic and Antioxidant Response to Grape Seed, Corn and Coconut Oils in Healthy Wistar Rats. Nutrients. 2017;9: pubmed publisher
    ..01). Hepatic fatty acid handling, but not antioxidant response, nor hepatic phytosterol deposition, could be related to a more efficient reverse-cholesterol transport in GSO-fed rats as compared to CO or CNO. ..
  5. Diaz J, Zamanillo D, Corbera J, Baeyens J, Maldonado R, Pericàs M, et al. Selective sigma-1 (sigma1) receptor antagonists: emerging target for the treatment of neuropathic pain. Cent Nerv Syst Agents Med Chem. 2009;9:172-83 pubmed
    ..Functional data in pain models are presented mainly on one series that provide evidence to consider selective sigma(1) receptor antagonists an innovative and alternative approach for treating neuropathic pain. ..
  6. Liu Z, Li H, Tan G, Tao Q, Ni W, Cheng X, et al. Identify mutation in amyotrophic lateral sclerosis cases using HaloPlex target enrichment system. Neurobiol Aging. 2014;35:2881.e11-2881.e15 pubmed publisher
    ..causative genes of ALS, including SOD1, SETX, FUS, ANG, TARDBP, ALS2, FIG4, VAPB, OPTN, DAO, VCP, UBQLN2, SPG11, SIGMAR1, DCTN1, SQSTM1, PFN1, and CHMP2B in 8 ALS probands. Using this approach, we got an average of 9...
  7. Mavlyutov T, Guo L, Epstein M, Ruoho A. Role of the Sigma-1 receptor in Amyotrophic Lateral Sclerosis (ALS). J Pharmacol Sci. 2015;127:10-6 pubmed publisher
    ..Possible mechanisms for regulation of MN excitability by S1R are discussed. ..
  8. Uchida N, Ujike H, Nakata K, Takaki M, Nomura A, Katsu T, et al. No association between the sigma receptor type 1 gene and schizophrenia: results of analysis and meta-analysis of case-control studies. BMC Psychiatry. 2003;3:13 pubmed
    ..An association study provided genetic evidence that the sigma receptor type 1 gene (SIGMAR1) was a possible susceptibility factor for schizophrenia, however, it was not replicated by a subsequent study...
  9. Almendra L, Laranjeira F, Fernández Marmiesse A, Negrão L. SIGMAR1 gene mutation causing Distal Hereditary Motor Neuropathy in a Portuguese family. Acta Myol. 2018;37:2-4 pubmed
    i>SIGMAR1 gene encodes a non-opioid endoplasmic reticulum (ER) protein which is involved in a large diversity of cell functions and is expressed ubiquitously in both central and peripheral nervous systems...
  10. Sachau J, Bruckmueller H, Gierthmühlen J, Magerl W, Kaehler M, Haenisch S, et al. SIGMA-1 Receptor Gene Variants Affect the Somatosensory Phenotype in Neuropathic Pain Patients. J Pain. 2019;20:201-214 pubmed publisher
    ..The sigma-1 receptor (SIGMAR1) is involved in pain modulation especially under pre-sensitized conditions...
  11. Takizawa R, Hashimoto K, Tochigi M, Kawakubo Y, Marumo K, Sasaki T, et al. Association between sigma-1 receptor gene polymorphism and prefrontal hemodynamic response induced by cognitive activation in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33:491-8 pubmed publisher
    ..Our findings also suggest that the prefrontal hemodynamic response assessed by noninvasive and less demanding NIRS is a useful intermediate phenotype for translational research in schizophrenia. ..
  12. Horga A, Tomaselli P, Gonzalez M, Laura M, Muntoni F, Manzur A, et al. SIGMAR1 mutation associated with autosomal recessive Silver-like syndrome. Neurology. 2016;87:1607-1612 pubmed
    ..limb spasticity (Silver-like syndrome) due to a mutation in the sigma nonopioid intracellular receptor-1 gene (SIGMAR1) and review the phenotypic spectrum of mutations in this gene...
  13. Satoh F, Miyatake R, Furukawa A, Suwaki H. Lack of association between sigma receptor gene variants and schizophrenia. Psychiatry Clin Neurosci. 2004;58:359-63 pubmed
    ..been reported between schizophrenia and two variants (GC-241-240TT and Gln2Pro) in the sigma(1) receptor gene (SIGMAR1). We also previously reported that, along with T-485 A, these two variants alter SIGMAR1 function...
  14. Ruscher K, Wieloch T. The involvement of the sigma-1 receptor in neurodegeneration and neurorestoration. J Pharmacol Sci. 2015;127:30-5 pubmed publisher
    ..Single nucleotide polymorphisms and mutations of the SIGMAR1 gene worsen outcome in Alzheimer's disease and myotrophic lateral sclerosis supporting a role of Sig-1R in ..
  15. Skuza G, Rogóz Z. Antidepressant-like effect of PRE-084, a selective sigma1 receptor agonist, in Albino Swiss and C57BL/6J mice. Pharmacol Rep. 2009;61:1179-83 pubmed
    ..These results support the idea that sigma(1)-receptors, but not sigma(2)-receptors, contribute to the mechanism of antidepressant activity of sigma agonists in FST. ..
  16. Watanabe S, Ilieva H, Tamada H, Nomura H, Komine O, Endo F, et al. Mitochondria-associated membrane collapse is a common pathomechanism in SIGMAR1- and SOD1-linked ALS. EMBO Mol Med. 2016;8:1421-1437 pubmed publisher
    ..mutation in the gene for sigma 1 receptor (Sig1R) is a cause of inherited juvenile amyotrophic lateral sclerosis (ALS16)...
  17. Ohi K, Hashimoto R, Yasuda Y, Fukumoto M, Yamamori H, Umeda Yano S, et al. The SIGMAR1 gene is associated with a risk of schizophrenia and activation of the prefrontal cortex. Prog Neuropsychopharmacol Biol Psychiatry. 2011;35:1309-15 pubmed publisher
    Several studies have identified the possible involvement of sigma non-opioid intracellular receptor 1 (SIGMAR1) in the pathogenesis of schizophrenia...
  18. Miki Y, Tanji K, Mori F, Wakabayashi K. Sigma-1 receptor is involved in degradation of intranuclear inclusions in a cellular model of Huntington's disease. Neurobiol Dis. 2015;74:25-31 pubmed publisher
    The sigma-1 receptor (SIGMAR1) is one of the endoplasmic reticulum (ER) chaperones, which participate in the degradation of misfolded proteins via the ER-related degradation machinery linked to the ubiquitin-proteasome pathway...
  19. Skuza G. Ethanol withdrawal-induced depressive symptoms in animals and therapeutic potential of sigma1 receptor ligands. Pharmacol Rep. 2013;65:1681-7 pubmed
    ..Moreover, the therapeutic potential of sigma1 receptor ligands for the treatment of depression disorder induced by ethanol abuse and withdrawal is discussed. ..
  20. Koriauli S, Natsvlishvili N, Barbakadze T, Mikeladze D. Knockdown of interleukin-10 induces the redistribution of sigma1-receptor and increases the glutamate-dependent NADPH-oxidase activity in mouse brain neurons. Biol Res. 2015;48:55 pubmed publisher
    ..In these conditions, glutamate-dependent ROS production is greatly increased leading to the initiation of apoptosis. In this circumstances, sigma-ligands could play a preventive role against NMDA receptor-mediated excitotoxicity. ..
  21. Kitanaka J, Kitanaka N, Tatsuta T, Hall F, Uhl G, Tanaka K, et al. Sigma1 receptor antagonists determine the behavioral pattern of the methamphetamine-induced stereotypy in mice. Psychopharmacology (Berl). 2009;203:781-92 pubmed publisher
  22. Pan L, Pasternak D, Xu J, Xu M, Lu Z, Pasternak G, et al. Isolation and characterization of alternatively spliced variants of the mouse sigma1 receptor gene, Sigmar1. PLoS ONE. 2017;12:e0174694 pubmed publisher
    ..The sigma1 receptor is encoded by the single copy SIGMAR1 gene...
  23. Balasuriya D, Stewart A, Crottès D, Borgese F, Soriani O, Edwardson J. The sigma-1 receptor binds to the Nav1.5 voltage-gated Na+ channel with 4-fold symmetry. J Biol Chem. 2012;287:37021-9 pubmed publisher
    ..Interestingly, two known Sig1R ligands, haloperidol and (+)-pentazocine, disrupted the Nav1.5/Sig1R interaction both in vitro and in living cells. Finally, we show that endogenously expressed Sig1R and Nav1.5 also functionally interact. ..
  24. Miyatake R, Furukawa A, Matsushita S, Higuchi S, Suwaki H. Functional polymorphisms in the sigma1 receptor gene associated with alcoholism. Biol Psychiatry. 2004;55:85-90 pubmed
    ..Two polymorphisms (GC-241-240TT and Gln2Pro) in the sigma1 receptor gene (SIGMAR1) have been identified...
  25. Tagashira H, Shinoda Y, Shioda N, Fukunaga K. Methyl pyruvate rescues mitochondrial damage caused by SIGMAR1 mutation related to amyotrophic lateral sclerosis. Biochim Biophys Acta. 2014;1840:3320-34 pubmed publisher
    Amyotrophic lateral sclerosis (ALS) is a disease caused by motor neuron degeneration. Recently, a novel SIGMAR1 gene variant (p.E102Q) was discovered in some familial ALS patients...
  26. Xu D, Yi W, Chen Y, Ma L, Wang J, Yu G. Overexpression of Sig1R is closely associated with tumor progression and poor outcome in patients with hilar cholangiocarcinoma. Med Oncol. 2014;31:261 pubmed publisher
    ..Our results suggest that Sig1R is frequently activated in human HC tissue and overexpression of Sig1R might serve as a predictor for tumor recurrence and a prognostic biomarker for HC patients. ..
  27. Abate C, Hornick J, Spitzer D, Hawkins W, Niso M, Perrone R, et al. Fluorescent derivatives of ? receptor ligand 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) as a tool for uptake and cellular localization studies in pancreatic tumor cells. J Med Chem. 2011;54:5858-67 pubmed publisher
    ..Fluorescent ?(2) ligands show their potential in clarifying the mechanisms of action of ?(2) receptors. ..
  28. Skrzycki M, Czeczot H. Multiple protective functions of sigma1 receptor. Curr Protein Pept Sci. 2014;15:798-811 pubmed
    ..This review describes influence of sigma1 receptor on various aspects of cellular metabolism, such as calcium signalling, mitochondrial functions, oxidative stress, survival and apoptotic pathways, and tumor cells proliferation. ..
  29. Bernard Marissal N, Médard J, Azzedine H, Chrast R. Dysfunction in endoplasmic reticulum-mitochondria crosstalk underlies SIGMAR1 loss of function mediated motor neuron degeneration. Brain. 2015;138:875-90 pubmed publisher
    Mutations in Sigma 1 receptor (SIGMAR1) have been previously identified in patients with amyotrophic lateral sclerosis and disruption of Sigmar1 in mouse leads to locomotor deficits...
  30. Macvicar T, Mannack L, Lees R, Lane J. Targeted siRNA Screens Identify ER-to-Mitochondrial Calcium Exchange in Autophagy and Mitophagy Responses in RPE1 Cells. Int J Mol Sci. 2015;16:13356-80 pubmed publisher
    ..These screens identified the ER chaperone and Ca2+ flux modulator, sigma non-opioid intracellular receptor 1 (SIGMAR1), as a regulator of autophagosome expansion during starvation...
  31. Soriani O, Rapetti Mauss R. Sigma 1 Receptor and Ion Channel Dynamics in Cancer. Adv Exp Med Biol. 2017;964:63-77 pubmed publisher
    b>SigmaR1 is a multitasking chaperone protein which has mainly been studied in CNS physiological and pathophysiological processes such as pain, memory, neurodegenerative diseases (amyotrophic lateral sclerosis , Parkinson's and Alzheimer's ..
  32. Laurini E, Marson D, Fermeglia M, Pricl S. 3D Homology Model of Sigma1 Receptor. Handb Exp Pharmacol. 2017;244:27-50 pubmed publisher
  33. Nandhagopal R, Meftah D, Al Kalbani S, Scott P. Recessive Distal Motor Neuropathy with Pyramidal signs in an Omani Kindred: Underlying Novel Mutation in the SIGMAR1 Gene. Eur J Neurol. 2017;: pubmed publisher
    Distal hereditary motor neuropathy (dHMN) due to sigma nonopiod intracellular receptor 1 gene (SIGMAR1) mutation (OMIM 601978...
  34. Avram S, Borcan F, Borcan L, Milac A, Mihailescu D. QSAR Approaches Applied to Antidepressants Induced Neurogenesis--in vivo and in silico Applications. Mini Rev Med Chem. 2015;16:230-40 pubmed
  35. Crottès D, Rapetti Mauss R, Alcaraz Pérez F, Tichet M, Gariano G, Martial S, et al. SIGMAR1 Regulates Membrane Electrical Activity in Response to Extracellular Matrix Stimulation to Drive Cancer Cell Invasiveness. Cancer Res. 2016;76:607-18 pubmed publisher
    ..Given the involvement of ion channels in promoting several hallmarks of cancer, our study also offers a potential strategy to therapeutically target ion channel function through Sig1R inhibition. ..
  36. Uchida N, Ujike H, Tanaka Y, Sakai A, Yamamoto M, Fujisawa Y, et al. A variant of the sigma receptor type-1 gene is a protective factor for Alzheimer disease. Am J Geriatr Psychiatry. 2005;13:1062-6 pubmed
    ..The authors provide here genetic evidence that the sigma receptor type 1 (SIGMAR1) gene is involved in susceptibility to AD.
  37. Tanji K, Miki Y, Maruyama A, Mimura J, Matsumiya T, Mori F, et al. Trehalose intake induces chaperone molecules along with autophagy in a mouse model of Lewy body disease. Biochem Biophys Res Commun. 2015;465:746-52 pubmed publisher
    ..Also, trehalose increased levels of several chaperon molecules, such as HSP90 and SigmaR1, in the brains of LBD model mice...
  38. Cobos E, Del Pozo E, Baeyens J. Irreversible blockade of sigma-1 receptors by haloperidol and its metabolites in guinea pig brain and SH-SY5Y human neuroblastoma cells. J Neurochem. 2007;102:812-25 pubmed
    ..These results suggest that HP may irreversibly inactivate sigma(1) receptors in guinea pig and human cells, probably after metabolism to reduced HP. ..
  39. Gueguinou M, Crottès D, Chantôme A, Rapetti Mauss R, Potier Cartereau M, Clarysse L, et al. The SigmaR1 chaperone drives breast and colorectal cancer cell migration by tuning SK3-dependent Ca2+ homeostasis. Oncogene. 2017;36:3640-3647 pubmed publisher
    ..Here, we report that SigmaR1, a stress-activated chaperone, is required to increase calcium influx by triggering the coupling between SK3, a ..
  40. Zhang X, Liu L, Jiang S, Zhong Y, Yang X. Activation of the ? receptor 1 suppresses NMDA responses in rat retinal ganglion cells. Neuroscience. 2011;177:12-22 pubmed publisher
    ..This effect of SKF could help ameliorate malfunction of GCs caused by excessive stimulation of NMDA receptors under pathological conditions. ..
  41. Friesland M, Mingorance L, Chung J, Chisari F, Gastaminza P. Sigma-1 receptor regulates early steps of viral RNA replication at the onset of hepatitis C virus infection. J Virol. 2013;87:6377-90 pubmed publisher
    ..Overall, our data indicate that the initial steps of HCV infection are regulated by S1R, a key component of MAMs, suggesting that these structures could serve as platforms for initial RNA replication during HCV infection. ..
  42. Skrzycki M, Czeczot H. Altered expression level of Sigma1 receptor gene in human colorectal cancer. J Recept Signal Transduct Res. 2013;33:313-8 pubmed publisher
    ..It is probably due to double nature of Sig1R action - in certain conditions it could act pro- or antiapoptotic. This action might depend on Sig1R activity resulting from its expression level. ..
  43. Dalvi P, Gupta V, Griffin B, O Brien Ladner A, Dhillon N. Ligand-Independent Activation of Platelet-Derived Growth Factor Receptor β during Human Immunodeficiency Virus-Transactivator of Transcription and Cocaine-Mediated Smooth Muscle Hyperplasia. Am J Respir Cell Mol Biol. 2015;53:336-45 pubmed publisher
    ..Finally, we report total abrogation of cocaine- and Tat-mediated synergistic increase in cell proliferation on inhibition of both ligand-dependent and ROS/Src-mediated ligand-independent phosphorylation of PDGFRβ. ..
  44. Lever J, Litton T, Fergason Cantrell E. Characterization of pulmonary sigma receptors by radioligand binding. Eur J Pharmacol. 2015;762:118-26 pubmed publisher
    ..2μmol/kg, a value near the recommended dosage for the drug as a cough suppressant. Overall, the present work provides a foundation for studies of drug interactions with pulmonary sigma1 and sigma2 receptors in vitro and in vivo. ..
  45. Ganapathy M, Prasad P, Huang W, Seth P, Leibach F, Ganapathy V. Molecular and ligand-binding characterization of the sigma-receptor in the Jurkat human T lymphocyte cell line. J Pharmacol Exp Ther. 1999;289:251-60 pubmed
    ..This splice variant was found to be nonfunctional in ligand binding assays. This constitutes the first report on the molecular characterization of the sigma-receptor in immune cells. ..
  46. Lee I, Chen S, Schetz J. An unambiguous assay for the cloned human sigma1 receptor reveals high affinity interactions with dopamine D4 receptor selective compounds and a distinct structure-affinity relationship for butyrophenones. Eur J Pharmacol. 2008;578:123-36 pubmed
    ..The antidepressant fluvoxamine, the drug of abuse methamphetamine, and the neurosteroid progesterone were amongst the many ligands whose interactions with the sigma(1) receptor were confirmed with our screening assay. ..
  47. Hayashi T, Fujimoto M. Detergent-resistant microdomains determine the localization of sigma-1 receptors to the endoplasmic reticulum-mitochondria junction. Mol Pharmacol. 2010;77:517-28 pubmed publisher
    ..These findings suggest that the MAM, bearing cholesterol and ceramide-enriched microdomains at the ER, may use the microdomains to anchor Sig-1Rs to the location; thus, it serves to stage Sig-1R at ER-mitochondria junctions. ..
  48. Ullah M, Ahmad A, Raza S, Amar A, Ali A, Bhatti A, et al. In silico analysis of SIGMAR1 variant (rs4879809) segregating in a consanguineous Pakistani family showing amyotrophic lateral sclerosis without frontotemporal lobar dementia. Neurogenetics. 2015;16:299-306 pubmed publisher
    ..members using microsatellite markers, and linkage was established with sigma non-opioid intracellular receptor 1 (SIGMAR1) gene at chromosome 9p13.2. Gene sequencing of SIGMAR1 revealed a novel 3'-UTR nucleotide variation c...
  49. Ivanova A, East M, Yi S, Kahn R. Characterization of recombinant ELMOD (cell engulfment and motility domain) proteins as GTPase-activating proteins (GAPs) for ARF family GTPases. J Biol Chem. 2014;289:11111-21 pubmed publisher
  50. Kim H, Kwon M, Choi W, Oh K, Oh S, Ki C, et al. Mutations in UBQLN2 and SIGMAR1 genes are rare in Korean patients with amyotrophic lateral sclerosis. Neurobiol Aging. 2014;35:1957.e7-8 pubmed publisher
    Mutations in the UBQLN2 and SIGMAR1 genes were recently identified in X-linked dominant amyotrophic lateral sclerosis and/or frontotemporal dementia (ALS and/or FTD) and FTD and/or motor neuron disease, respectively...
  51. Valenza M, DiLeo A, Steardo L, Cottone P, Sabino V. Ethanol-related behaviors in mice lacking the sigma-1 receptor. Behav Brain Res. 2016;297:196-203 pubmed publisher
    ..We used an extensive panel of behavioral tests to examine ethanol actions in male, adult mice lacking Oprs1, the gene encoding the Sig-1R...
  52. Koroglu C, Yilmaz R, Sorgun M, Solakoglu S, Sener O. GNE missense mutation in recessive familial amyotrophic lateral sclerosis. Neurogenetics. 2017;18:237-243 pubmed publisher
    ..We also Sanger sequenced all coding sequences of SIGMAR1, a gene reported as responsible for juvenile ALS in a family. We did not find any mutation in SIGMAR1...
  53. Wang L, Duncan G. Silencing of sigma-1 receptor induces cell death in human lens cells. Exp Cell Res. 2006;312:1439-46 pubmed
    ..These increases were inhibited in the cells where knockdown had occurred but not in cells exposed to scrambled siRNA. This study establishes a central role for Sig-1R in cell survival and death. ..
  54. Prause J, Goswami A, Katona I, Roos A, Schnizler M, Bushuven E, et al. Altered localization, abnormal modification and loss of function of Sigma receptor-1 in amyotrophic lateral sclerosis. Hum Mol Genet. 2013;22:1581-600 pubmed publisher
    ..Finally, pharmacological activation of SigR1 induced the clearance of mutant protein aggregates in these cells. Our results support the notion that SigR1 is abnormally modified and contributes to the pathogenesis of ALS. ..
  55. Schmidt H, Zheng S, Gurpinar E, Koehl A, Manglik A, Kruse A. Crystal structure of the human ?1 receptor. Nature. 2016;532:527-30 pubmed publisher
    ..Taken together, these results reveal the overall architecture, oligomerization state, and molecular basis for ligand recognition by this important but poorly understood protein. ..
  56. Aydar E, Stratton D, Fraser S, Djamgoz M, Palmer C. Sigma-1 receptors modulate neonatal Nav1.5 ion channels in breast cancer cell lines. Eur Biophys J. 2016;45:671-683 pubmed
    ..Overall, these results are consistent with the idea of a sigma-1 protein behaving like either a "chaperone" or a regulatory subunit associated with nNav1.5. ..
  57. Brimson J, Brown C, Safrany S. Antagonists show GTP-sensitive high-affinity binding to the sigma-1 receptor. Br J Pharmacol. 2011;164:772-80 pubmed publisher
    ..This interaction is only observed when analysing antagonist binding. The identity of the G protein remains to be resolved. The concept of agonist and antagonist at the sigma-1 receptor needs to be revisited. ..
  58. Fehér A, Juhász A, Laszlo A, Pakaski M, Kalman J, Janka Z. Association between a variant of the sigma-1 receptor gene and Alzheimer's disease. Neurosci Lett. 2012;517:136-9 pubmed publisher
    ..A number of investigations support the possible involvement of sigma non-opioid intracellular receptor 1 (SIGMAR1) in the pathophysiology of AD...
  59. Li X, Hu Z, Liu L, Xie Y, Zhan Y, Zi X, et al. A SIGMAR1 splice-site mutation causes distal hereditary motor neuropathy. Neurology. 2015;84:2430-7 pubmed publisher
    ..Sequencing of these 3 variants in family members revealed the c.151+1G>T mutation in SIGMAR1 gene, which located in homozygous region spanning approximately 5.3 Mb at chromosome 9p13.1-p13...
  60. Calabrò M, Porcelli S, Crisafulli C, Wang S, Lee S, Han C, et al. Genetic Variants Within Molecular Targets of Antipsychotic Treatment: Effects on Treatment Response, Schizophrenia Risk, and Psychopathological Features. J Mol Neurosci. 2018;64:62-74 pubmed publisher
    ..that CHRNA7 and HTR2A genes may modulate both positive and negative symptoms responses, while PLA2G4A and SIGMAR1 may modulate respectively positive and negative symptoms responses...
  61. Xu Q, Li E, Zhang Y, Liao L, Xu X, Wu Z, et al. Overexpression of sigma1 receptor and its positive associations with pathologic TNM classification in esophageal squamous cell carcinoma. J Histochem Cytochem. 2012;60:457-66 pubmed publisher
    Sigma1 receptor (sigma1R), a significant protein, has been found to be frequently upregulated in human tumor cells and tissues. It has been demonstrated that sigma1R is involved in proliferation and adhesion of cancer cells...
  62. Watanabe Y, Nunokawa A, Kaneko N, Shibuya M, Egawa J, Someya T. Supportive evidence for the association between the Gln2Pro polymorphism in the SIGMAR1 gene and schizophrenia in the Japanese population: a case-control study and an updated meta-analysis. Schizophr Res. 2012;141:279-80 pubmed publisher
  63. Mavliutov T. [Protective function of sigma-1 receptor in spinal cord motor neurons]. Tsitologiia. 2013;55:285-9 pubmed
    ..In this review we consider the possible pathways by which the sigma-1 receptor may reduce the excitability of motoneurons and thereby play a protective function during the progression of ALS. ..
  64. Kishi T, Yoshimura R, Okochi T, Fukuo Y, Kitajima T, Okumura T, et al. Association analysis of SIGMAR1 with major depressive disorder and SSRI response. Neuropharmacology. 2010;58:1168-73 pubmed publisher
    ..To evaluate the association of sigma 1 receptor gene (SIGMAR1) and MDD and SSRIs therapeutic response in MDD, we conducted a case-control study of Japanese samples (466 MDD ..
  65. Dalvi P, Wang K, Mermis J, Zeng R, Sanderson M, Johnson S, et al. HIV-1/cocaine induced oxidative stress disrupts tight junction protein-1 in human pulmonary microvascular endothelial cells: role of Ras/ERK1/2 pathway. PLoS ONE. 2014;9:e85246 pubmed publisher
  66. Kringel D, Ultsch A, Zimmermann M, Jansen J, Ilias W, Freynhagen R, et al. Emergent biomarker derived from next-generation sequencing to identify pain patients requiring uncommonly high opioid doses. Pharmacogenomics J. 2017;17:419-426 pubmed publisher
    ..Following precisely calculated selection of the 34 most informative markers in the OPRM1, OPRK1, OPRD1 and SIGMAR1 genes, pattern of genotypes belonging to either patient group could be derived using a k-nearest neighbor (kNN) ..
  67. Dussossoy D, Carayon P, Belugou S, Feraut D, Bord A, Goubet C, et al. Colocalization of sterol isomerase and sigma(1) receptor at endoplasmic reticulum and nuclear envelope level. Eur J Biochem. 1999;263:377-86 pubmed
    ..Taken together our results suggest that both SR31747A-binding proteins not only play a role in sterol metabolism but indirectly affect lipoprotein functions. ..
  68. Vollrath J, Sechi A, Dreser A, Katona I, Wiemuth D, Vervoorts J, et al. Loss of function of the ALS protein SigR1 leads to ER pathology associated with defective autophagy and lipid raft disturbances. Cell Death Dis. 2014;5:e1290 pubmed publisher
    ..Taken together, our results support the notion that loss of SigR1 function contributes to ALS pathology by causing abnormal ER morphology, lipid raft destabilization and defective endolysosomal pathways. ..
  69. Gregianin E, Pallafacchina G, Zanin S, Crippa V, Rusmini P, Poletti A, et al. Loss-of-function mutations in the SIGMAR1 gene cause distal hereditary motor neuropathy by impairing ER-mitochondria tethering and Ca2+ signalling. Hum Mol Genet. 2016;25:3741-3753 pubmed publisher
    ..segment detection and whole-exome sequencing approaches, we identified two novel homozygous mutations in the SIGMAR1 gene (p.E138Q and p.E150K) in two distinct Italian families affected by an autosomal recessive form of HMN...
  70. Alam S, Abdullah C, Aishwarya R, Orr A, Traylor J, Miriyala S, et al. Sigmar1 regulates endoplasmic reticulum stress-induced C/EBP-homologous protein expression in cardiomyocytes. Biosci Rep. 2017;37: pubmed publisher
    ..Here, we examined a novel function of Sigma 1 receptor (Sigmar1) in regulating CHOP expression under ER stress in cardiomyocytes...
  71. Sun B, Kawahara M, Nagamune T. Modeling tandem AAG8-MEK inhibition in melanoma cells. Cancer Med. 2014;3:710-8 pubmed publisher
    ..Aging-associated gene 8 (AAG8, encoded by the SIGMAR1 gene) is a chaperone protein profoundly elaborated in neurology...
  72. Kim F, Maher C. Sigma1 Pharmacology in the Context of Cancer. Handb Exp Pharmacol. 2017;244:237-308 pubmed publisher
    ..several fundamental questions regarding drug mechanism of action and the physiological relevance of aberrant SIGMAR1 transcript and Sigma1 protein expression in certain cancers remain unanswered or only partially answered...
  73. Maruszak A, Safranow K, Gacia M, Gabryelewicz T, Słowik A, Styczynska M, et al. Sigma receptor type 1 gene variation in a group of Polish patients with Alzheimer's disease and mild cognitive impairment. Dement Geriatr Cogn Disord. 2007;23:432-8 pubmed
    The sigma-1 receptor (SIGMAR1) is a subtype of a nonopioid sigma receptor family and is implicated in numerous functions connected with Alzheimer's disease (AD)...
  74. Fukunaga K, Shinoda Y, Tagashira H. The role of SIGMAR1 gene mutation and mitochondrial dysfunction in amyotrophic lateral sclerosis. J Pharmacol Sci. 2015;127:36-41 pubmed publisher
    ..Recently, it was reported that familial ALS patients exhibit a missense mutation in SIGMAR1 (c...
  75. Skrzycki M, Czeczot H, Mielczarek Puta M, Otto Ślusarczyk D, Graboń W. Effect of different concentrations of oxygen on expression of sigma 1 receptor and superoxide dismutases in human colon adenocarcinoma cell lines. J Recept Signal Transduct Res. 2017;37:252-258 pubmed publisher
    ..Studied proteins are involved in intracellular response to stress related with different concentrations of oxygen. ..
  76. Prasad P, Li H, Fei Y, Ganapathy M, Fujita T, Plumley L, et al. Exon-intron structure, analysis of promoter region, and chromosomal localization of the human type 1 sigma receptor gene. J Neurochem. 1998;70:443-51 pubmed
  77. Miki Y, Mori F, Kon T, Tanji K, Toyoshima Y, Yoshida M, et al. Accumulation of the sigma-1 receptor is common to neuronal nuclear inclusions in various neurodegenerative diseases. Neuropathology. 2014;34:148-58 pubmed publisher
    The sigma-1 receptor (SIGMAR1) is now known to be one of the endoplasmic reticulum (ER) chaperones, which participate in the degradation of misfolded proteins in cells via the ER-related degradation machinery linked to the ubiquitin-..
  78. Gris G, Cobos E, Zamanillo D, Portillo Salido E. Sigma-1 receptor and inflammatory pain. Inflamm Res. 2015;64:377-81 pubmed publisher
    ..These recent studies are summarized in the present commentary. Central and peripheral pharmacological blockade of Sig-1R could be an effective option to treat inflammatory pain. ..
  79. Ben Ami O, Kinor N, Perelman A, Yadid G. Dopamine-1 receptor agonist, but not cocaine, modulates sigma(1) gene expression in SVG cells. J Mol Neurosci. 2006;29:169-76 pubmed
    ..This (+)-SKF38393-induced effect was blocked by the D(1)R selective antagonist (+)-SCH23390. These results suggest that the effect of cocaine on sigma(1) gene expression in the brain might be indirect and mediated through D(1)R. ..
  80. Schrock J, Spino C, Longen C, Stabler S, Marino J, Pasternak G, et al. Sequential cytoprotective responses to Sigma1 ligand-induced endoplasmic reticulum stress. Mol Pharmacol. 2013;84:751-62 pubmed publisher
    ..Together, these data suggest that UPR and autophagy are engaged as primary and secondary cytoprotective responses, respectively, to Sigma1 ligand-induced disruption of cancer cell protein homeostasis. ..
  81. Mori T, Hayashi T, Hayashi E, SU T. Sigma-1 receptor chaperone at the ER-mitochondrion interface mediates the mitochondrion-ER-nucleus signaling for cellular survival. PLoS ONE. 2013;8:e76941 pubmed publisher
    ..Therefore, the ER-mitochondrion interface serves as an important subcellular entity in the regulation of cellular survival by enhancing the stress-responding signaling between mitochondria, ER, and nucleus. ..
  82. Lövkvist H, Jönsson A, Luthman H, Jood K, Jern C, Wieloch T, et al. Variations in apolipoprotein D and sigma non-opioid intracellular receptor 1 genes with relation to risk, severity and outcome of ischemic stroke. BMC Neurol. 2014;14:191 pubmed publisher
    In experimental studies, the apolipoprotein D (APOD) and the sigma receptor type 1 (SIGMAR1) have been related to processes of brain damage, repair and plasticity...
  83. Maher C, Thomas J, Haas D, Longen C, Oyer H, Tong J, et al. Small-Molecule Sigma1 Modulator Induces Autophagic Degradation of PD-L1. Mol Cancer Res. 2018;16:243-255 pubmed publisher
    Emerging evidence suggests that Sigma1 (SIGMAR1, also known as sigma-1 receptor) is a unique ligand-regulated integral membrane scaffolding protein that contributes to cellular protein and lipid homeostasis...
  84. Ortega Roldan J, Ossa F, Schnell J. Characterization of the human sigma-1 receptor chaperone domain structure and binding immunoglobulin protein (BiP) interactions. J Biol Chem. 2013;288:21448-57 pubmed publisher
  85. Balasuriya D, D Sa L, Talker R, Dupuis E, Maurin F, Martin P, et al. A direct interaction between the sigma-1 receptor and the hERG voltage-gated K+ channel revealed by atomic force microscopy and homogeneous time-resolved fluorescence (HTRF®). J Biol Chem. 2014;289:32353-63 pubmed publisher
    ..We suggest that the sigma-1 receptor may bind to hERG in the endoplasmic reticulum, aiding its assembly and trafficking to the plasma membrane. ..
  86. Hayashi T. Sigma-1 receptor: the novel intracellular target of neuropsychotherapeutic drugs. J Pharmacol Sci. 2015;127:2-5 pubmed publisher
    ..The sigma-1 receptor may thus provide an intracellular drug target that enables controlling ER stress and free radical generation under pathological conditions. ..
  87. Thomas J, Longen C, Oyer H, Chen N, Maher C, Salvino J, et al. Sigma1 Targeting to Suppress Aberrant Androgen Receptor Signaling in Prostate Cancer. Cancer Res. 2017;77:2439-2452 pubmed publisher
    ..2017 aacr. ..
  88. Balasuriya D, Stewart A, Edwardson J. The ?-1 receptor interacts directly with GluN1 but not GluN2A in the GluN1/GluN2A NMDA receptor. J Neurosci. 2013;33:18219-24 pubmed publisher
    ..We conclude that the Sig1R binds to the GluN1/GluN2A NMDAR specifically via the GluN1 subunit. This interaction likely accounts for at least some of the modulatory effects of Sig1R ligands on the NMDAR. ..
  89. Maurice T, Grégoire C, Espallergues J. Neuro(active)steroids actions at the neuromodulatory sigma1 (sigma1) receptor: biochemical and physiological evidences, consequences in neuroprotection. Pharmacol Biochem Behav. 2006;84:581-97 pubmed
    ..Biochemical and physiological arguments for an interaction of neuro(active)steroids with the sigma(1) receptor are analyzed and the impact on physiopathological outcomes in neuroprotection is illustrated. ..
  90. Das D, Persaud L, Dejoie J, Happy M, Brannigan O, De Jesus D, et al. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) activates caspases in human prostate cancer cells through sigma 1 receptor. Biochem Biophys Res Commun. 2016;470:319-323 pubmed publisher
    ..These results indicate that Sig1R could represent a promising molecule to sensitize human breast cancers to TRAIL. Collectively, these studies define Sig1R as a key mediator of TRAIL induction of cancer-specific killing. ..
  91. Li J, Liu B, Gao X, Ma Z, Caosong T, Mei Y, et al. Overexpression of sigma-1 receptor inhibits ADAM10 and ADAM17 mediated shedding in vitro. Protein Cell. 2012;3:153-9 pubmed publisher
    ..Our results indicate that sigma-1 receptor plays an important role in modifying the function of transmembrane proteases. ..