Ask about this productRelated genes to: SIGMAR1 antibody
- Gene:
- SIGMAR1 NIH gene
- Name:
- sigma non-opioid intracellular receptor 1
- Previous symbol:
- OPRS1
- Synonyms:
- SR-BP1
- Chromosome:
- 9p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 1993-03-11
- Date modifiied:
- 2014-11-19
Related products to: SIGMAR1 antibody
Related articles to: SIGMAR1 antibody
- - Source: PubMed
Publication date: 2026/04/07
Özenç BetülAkpek BurakAteş Başak E - One of the biggest causes of cancer-related mortality worldwide is still colon adenocarcinoma (COAD). Therefore, it is essential to investigate new therapy strategies. This study presents a multi-scale, hypothesis-generating framework that integrates network pharmacology with multi-omics data and quantum chemical analyses to systematically explore the repositioning potential of amodiaquine and desethylamodiaquine in colon adenocarcinoma. Eleven gene targets that were found to be shared across medication, gene expression, and illness databases included several computationally significant central hub genes with high network centrality, including BTK, SIGMAR1, SYK, and KCNH2. Amodiaquine and Desethylamodiaquine both showed high binding scores (-7.9 to -12.6 kcal·mol⁻¹) across all the selected proteins. The protein-ligand complexes' structural stability was confirmed by molecular dynamic simulations lasting more than 100 ns; RMSD, RMSF, and radius of gyration analyses collectively indicate that the protein-ligand complexes maintain structural stability, compactness, and limited conformational fluctuation throughout the simulation, reflecting preserved protein integrity rather than direct binding strength. While density functional theory investigations indicated stable geometries with high electronic polarizability, MM-PBSA calculations yielded binding free energies within a range of ΔG_bind = -59.0 to -67.0 kcal·mol⁻¹ . These results suggest that amodiaquine derivatives have anti-COAD actions due to their disruption of important immune-regulatory and apoptotic pathways. These findings computationally prioritize amodiaquine and desethylamodiaquine as candidate multi-target interactors in colon adenocarcinoma, warranting further experimental investigation rather than implying established therapeutic efficacy. - Source: PubMed
Publication date: 2026/03/06
Kurmi Santosh Prasad ChaudharyFayek Fady HMishra Vipin KumarNagaraja SreeharshaKn AnithaThapa ShankarKurmi Suneel KumarGupta Roma Kumari - Opioids are potent analgesics and sedative compounds that acts primarily through opioid receptor (ORs) as µOR, δOR, κOR. Beyond their well-established roles in pain management, mood regulation, respiratory control, and ionic homeostasis, opioids are increasingly recognized for their modulating neuroinflammation via receptor-mediated pathways influencing glial activity and inflammatory signaling. The present study aimed to comparatively evaluate the pharmacokinetic profile and receptor-binding affinities of five natural opioids including morphine, codeine, noscapine, papaverine, and thebaine with a focus on their therapeutic efficacy, safety profile, and molecular targets implicated in opioid-mediated neuroinflammation to identify promising candidates for effective therapeutic intervention. Through integrative computational approaches including molecular docking, ADMET analysis, and network pharmacology, the study revealed favourable absorption and distribution for all compounds, though, morphine, noscapine, and papaverine exhibited potential toxicity. Differences in metabolism and excretion suggested variable pharmacokinetics. GO and KEGG analyses revealed involvement in calcium channel activity, neurotransmitter regulation, and dopaminergic synapse signaling. Protein Protein Interaction (PPI) network highlighted DRD2, OPRM1, and SIGMAR1 as key hub genes. Molecular docking showed noscapine, papaverine, and morphine had the highest affinity for µOR; morphine, codeine, and thebaine for δOR; and noscapine, papaverine, and thebaine for κOR. OPRM1 emerged as the primary target, followed by SIGMAR1 and DRD2. MD simulation suggest receptor's structural stability, supporting their potential to engage DRD2 in biologically relevant conformational states. The comparative analysis underscores the distinct pharmacological profiles of natural opioids and identifies potential molecular targets for developing safer, neuroinflammation-focused opioid therapies. - Source: PubMed
Publication date: 2026/02/17
Gaglani PratikkumarSharma ShaliniSrivastava AtulPandey VinitaYadav VandanaSoni Subhashini - Previous studies have shown that SIGMAR1/Sigma-1 receptor (sigma non-opioid intracellular receptor 1) provides protective effects against lipopolysaccharide (LPS)-induced acute lung injury (ALI), however the underlying mechanism remains unclear. A recent study highlighted SIGMAR1's protective role against ferroptosis but did not fully elucidate the mechanism involved. Endothelial ferroptosis, which significantly affects microvascular permeability, has garnered increasing attention in research. In this context, we aimed to investigate how SIGMAR1 mitigates endothelial ferroptosis in ALI induced by LPS. PRE-084 (SIGMAR1 activator) inhibited endothelial ferroptosis and microvascular hyperpermeability in ALI induced by LPS; however, this effect was blocked by mitophagy inhibition. Knockout of worsened microvascular hyperpermeability and endothelial ferroptosis, but these effects were mitigated by activating SIRT3 (sirtuin 3). Conversely, inhibiting SIRT3 blocked the upregulation of SIGMAR1-mediated mitophagy and limited endothelial ferroptosis in ALI induced by LPS. In addition, LPS exposure led to the acetylation of lysine 498 in ATP5F1A/ATP5A1 (ATP synthase F1 subunit alpha). Importantly, downregulating ATP5F1A acetylation prevented the SIRT3 inhibition from blocking the effects of SIGMAR1 in facilitating mitophagy and preventing ferroptosis. Interestingly, downregulating ATP5F1A acetylation or activation of SIRT3 did not alter the effects of PRE-084 on ALI when mitophagy was inhibited, suggesting that SIGMAR1's ALI protective effects involve ATP5F1A- or SIRT3-dependent mitophagy. In conclusion, our findings indicate that SIGMAR1 alleviates endothelial ferroptosis and microvascular hyperpermeability in LPS-induced ALI through SIRT3-mediated mitophagy. Furthermore, the deacetylation of ATP5F1A at lysine 498 by SIRT3 is essential for SIGMAR1-mediated PRKN/parkin-dependent mitophagy.: ALI, acute lung injury; ARDS, acute respiratory distress syndrome; ATP, adenosine triphosphate; ATP5F1A, ATP synthase F1 subunit alpha; BCA, bicinchoninic acid; EB, Evans blue dye; ECM, endothelial cell medium; FBS, fetal bovine serum; FITC, fluorescein isothiocyanate; Fer-1, ferrostatin-1; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GFP-LC3, green fluorescent protein-microtubule associated protein 1 light chain 3 alpha; GPX4, glutathione peroxidase 4; GSH, glutathione; GSSG, glutathione disulfide; KO, knockout; LPS, lipopolysaccharide; LRRK2, leucine rich repeat kinase 2; MDA, malondialdehyde; MPMVECs, mouse pulmonary microvascular endothelial cells; MTT, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide; PBS, phosphate-buffered saline; PECAM1/CD31, platelet and endothelial cell adhesion molecule 1; PRKN, parkin RBR E3 uniquitin protein ligase; ROS, reactive oxygen species; RSL3, RAS-selective lethal 3; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SIGMAR1, sigma non-opioid intracellular receptor 1; SIRT3, sirtuin 3; siRNA, small interfering RNA; TUNEL, terminal deoxyribonucleotidyl transferase-mediated deoxyuridine 5-triphosphate-digoxigenin nick end labeling; VHP, vascular hyperpermeability; W:D, wet:dry; WT, wild type. - Source: PubMed
Publication date: 2026/02/19
Gao FeiLi ZhiwangPeng TianLin BoWang XiangDai XinguiAi ChenmuLi GuichengYang FengLin XianzhongZhang YunLi Tao - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by progressive degeneration of upper and lower motor neurons. Most forms of ALS associated with a suspected causal variant are inherited in an autosomal dominant manner. However, there is an important subset of autosomal recessive (AR) variants, often associated with early-onset or atypical clinical features. Advances in genetic sequencing have led to increased recognition of AR ALS. In this review, we focus on four key confirmed AR ALS-associated genes, which appear to be most common-, , , and the D90A variant of -reviewing their pathophysiology and unique clinical manifestations. We also highlight very rare AR mutations implicated in ALS, including , , and , and some associated with overlap syndromes or debated pathogenicity including , , and These genes are involved in an array of processes including axonal transport, endosomal trafficking, oxidative stress response, and autophagy, suggesting distinct mechanisms of motor neuron degeneration. Some forms of AR ALS more frequently present with juvenile onset and slower progression, but other genes are associated with broader phenotypic spectra. This includes overlap with hereditary spastic paraplegia (HSP) and hereditary ataxias. Understanding these AR forms of ALS may enhance diagnostic precision, improve prognostication, and may pave the way for targeted gene therapies. This review underscores the emerging significance of AR inheritance in ALS and calls for deeper investigation into its molecular and clinical dimensions. - Source: PubMed
Publication date: 2026/01/27
Allen Matti DDiab VanessaLezaic NastasijaBinet MayaGentil Benoit JBlanchard OliverGenge AngelaMassie Rami