σ 受体的分子功能：过去、现在和未来。
The Molecular Function of σ Receptors: Past, Present, and Future.
机构信息
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Trends Pharmacol Sci. 2019 Sep;40(9):636-654. doi: 10.1016/j.tips.2019.07.006. Epub 2019 Aug 3.
Abstract
The σ and σ receptors are enigmatic proteins that have attracted attention for decades due to the chemical diversity and therapeutic potential of their ligands. However, despite ongoing clinical trials with σ receptor ligands for multiple conditions, relatively little is known regarding the molecular function of these receptors. In this review, we revisit past research on σ receptors and discuss the interpretation of these data in light of recent developments. We provide a synthesis of emerging structural and genetic data on the σ receptor and discuss the recent cloning of the σ receptor. Finally, we discuss the major questions that remain in the study of σ receptors.
摘要
σ 和 σ 受体是神秘的蛋白质，由于其配体的化学多样性和治疗潜力，它们引起了人们数十年的关注。然而，尽管有针对多种疾病的 σ 受体配体的临床试验在进行，但对于这些受体的分子功能相对知之甚少。在这篇综述中，我们回顾了过去关于 σ 受体的研究，并根据最近的发展讨论了这些数据的解释。我们提供了 σ 受体的新兴结构和遗传数据的综合，并讨论了 σ 受体的最近克隆。最后，我们讨论了 σ 受体研究中仍然存在的主要问题。
相似文献
1
The Molecular Function of σ Receptors: Past, Present, and Future.σ 受体的分子功能：过去、现在和未来。
Trends Pharmacol Sci. 2019 Sep;40(9):636-654. doi: 10.1016/j.tips.2019.07.006. Epub 2019 Aug 3.
2
Small-Molecule Modulators of Sigma1 and Sigma2/TMEM97 in the Context of Cancer: Foundational Concepts and Emerging Themes.癌症背景下西格玛1和西格玛2/TMEM97的小分子调节剂：基础概念与新出现的主题
Front Pharmacol. 2019 Oct 21;10:1141. doi: 10.3389/fphar.2019.01141. eCollection 2019.
3
Sigma receptor research: progress towards diagnostic and therapeutic uses of sigma ligands.西格玛受体研究：西格玛配体在诊断和治疗应用方面的进展。
Curr Pharm Des. 2012;18(7):861-2. doi: 10.2174/138161212799436502.
4
Synthesis, in vitro and in vivo characterization of new benzoxazole and benzothiazole-based sigma receptor ligands.新型苯并恶唑和苯并噻唑类sigma 受体配体的合成、体外和体内特征研究。
Eur J Med Chem. 2019 Jul 15;174:226-235. doi: 10.1016/j.ejmech.2019.04.056. Epub 2019 Apr 21.
5
Structural Insights into Sigma1 Function.对西格玛1功能的结构见解
Handb Exp Pharmacol. 2017;244:13-25. doi: 10.1007/164_2016_95.
6
Structural basis for σ receptor ligand recognition.σ 受体配体识别的结构基础。
Nat Struct Mol Biol. 2018 Oct;25(10):981-987. doi: 10.1038/s41594-018-0137-2. Epub 2018 Oct 5.
7
Antiproliferative and cytotoxic effects of some sigma2 agonists and sigma1 antagonists in tumour cell lines.某些σ2激动剂和σ1拮抗剂对肿瘤细胞系的抗增殖和细胞毒性作用。
Naunyn Schmiedebergs Arch Pharmacol. 2004 Aug;370(2):106-13. doi: 10.1007/s00210-004-0961-2. Epub 2004 Jul 31.
8
Introduction to Sigma Proteins: Evolution of the Concept of Sigma Receptors.西格玛蛋白简介：西格玛受体概念的演变
Handb Exp Pharmacol. 2017;244:1-11. doi: 10.1007/164_2017_41.
9
Recent Advances in the Development of Sigma Receptor Ligands as Cytotoxic Agents: A Medicinal Chemistry Perspective.近年来，作为细胞毒剂的 sigma 受体配体的发展进展：药物化学视角。
J Med Chem. 2021 Jun 24;64(12):7926-7962. doi: 10.1021/acs.jmedchem.0c02265. Epub 2021 Jun 2.
10
Potential antidepressant activity of sigma ligands.西格玛配体的潜在抗抑郁活性。
Pol J Pharmacol. 2003 Nov-Dec;55(6):923-34.
引用本文的文献
1
Could R-Ketamine and Wolfram Syndrome Inform Understanding of Depression and Suicidality? A Sigma-1 Receptor-Based Perspective.R-氯胺酮和沃夫勒姆综合征能否为理解抑郁症和自杀倾向提供线索？基于西格玛-1受体的视角。
Hum Psychopharmacol. 2025 Sep;40(5):e70019. doi: 10.1002/hup.70019.
2
Integrated control of cancer stemness by σ receptor in advanced prostate cancer.σ受体对晚期前列腺癌中癌症干性的综合调控
Oncogene. 2025 Sep 2. doi: 10.1038/s41388-025-03541-7.
3
Conserved LIR-specific interaction of Sigma-1 receptor and GABARAP.Sigma-1受体与GABARAP的保守性LIR特异性相互作用。
iScience. 2025 Aug 5;28(9):113287. doi: 10.1016/j.isci.2025.113287. eCollection 2025 Sep 19.
4
Choline-An Essential Nutrient with Health Benefits and a Signaling Molecule.胆碱——一种具有健康益处的必需营养素及信号分子。
Int J Mol Sci. 2025 Jul 24;26(15):7159. doi: 10.3390/ijms26157159.
5
Sigma1 Receptor Modulates Plasma Membrane and Mitochondrial Peroxiporins.西格玛1受体调节质膜和线粒体过氧化物孔蛋白。
Cells. 2025 Jul 15;14(14):1082. doi: 10.3390/cells14141082.
6
Activation of Sigma 1 Receptor Preserves Visual Function After Optic Nerve Injury.σ1受体激活可在视神经损伤后保留视觉功能。
Invest Ophthalmol Vis Sci. 2025 Jul 1;66(9):13. doi: 10.1167/iovs.66.9.13.
7
Recent Advances in the Development of Sigma Receptor (Radio)Ligands and Their Application in Tumors.σ受体（放射性）配体的开发进展及其在肿瘤中的应用
ACS Pharmacol Transl Sci. 2025 Mar 7;8(4):951-977. doi: 10.1021/acsptsci.4c00711. eCollection 2025 Apr 11.
8
Preclinical Profile of CM699 as a Medication Candidate for Stimulant Use Disorder.CM699作为兴奋剂使用障碍治疗候选药物的临床前概况
ACS Chem Neurosci. 2025 Apr 16;16(8):1454-1468. doi: 10.1021/acschemneuro.4c00589. Epub 2025 Mar 25.
9
Sigma-1 Receptor Modulates CFA-Induced Inflammatory Pain via Sodium Channels in Small DRG Neurons.西格玛-1受体通过小直径背根神经节神经元中的钠通道调节弗氏完全佐剂诱导的炎性疼痛。
Biomolecules. 2025 Jan 6;15(1):73. doi: 10.3390/biom15010073.
10
Sertraline modulates hippocampal plasticity via sigma 1 receptors, cellular stress and neurosteroids.舍曲林通过 sigma 1 受体、细胞应激和神经甾体调节海马可塑性。
Transl Psychiatry. 2024 Nov 21;14(1):474. doi: 10.1038/s41398-024-03185-3.
本文引用的文献
1
Modulation of the sigma-1 receptor-IRE1 pathway is beneficial in preclinical models of inflammation and sepsis.调节 sigma-1 受体-IRE1 通路对炎症和脓毒症的临床前模型有益。
Sci Transl Med. 2019 Feb 6;11(478). doi: 10.1126/scitranslmed.aau5266.
2
A phase 1 clinical trial of the sigma-2 receptor complex allosteric antagonist CT1812, a novel therapeutic candidate for Alzheimer's disease.一项针对新型阿尔茨海默病治疗候选药物sigma-2受体复合物变构拮抗剂CT1812的1期临床试验。
Alzheimers Dement (N Y). 2019 Jan 23;5:20-26. doi: 10.1016/j.trci.2018.11.001. eCollection 2019.
3
TMEM97 and PGRMC1 do not mediate sigma-2 ligand-induced cell death.跨膜蛋白97（TMEM97）和孕酮受体膜组分1（PGRMC1）不介导σ-2配体诱导的细胞死亡。
Cell Death Discov. 2019 Jan 28;5:58. doi: 10.1038/s41420-019-0141-2. eCollection 2019.
4
Choline Is an Intracellular Messenger Linking Extracellular Stimuli to IP-Evoked Ca Signals through Sigma-1 Receptors.胆碱是一种细胞内信使，通过西格玛-1 受体将细胞外刺激与 IP 诱发的 Ca 信号联系起来。
Cell Rep. 2019 Jan 8;26(2):330-337.e4. doi: 10.1016/j.celrep.2018.12.051.
5
SKF-10047, a prototype Sigma-1 receptor agonist, augmented the membrane trafficking and uptake activity of the serotonin transporter and its C-terminus-deleted mutant via a Sigma-1 receptor-independent mechanism.SKF-10047，一种西格玛-1 受体激动剂原型，通过一种不依赖西格玛-1 受体的机制增强了 5-羟色胺转运体及其 C 端缺失突变体的膜转运和摄取活性。
J Pharmacol Sci. 2019 Jan;139(1):29-36. doi: 10.1016/j.jphs.2018.11.005. Epub 2018 Nov 24.
6
Structural basis for σ receptor ligand recognition.σ 受体配体识别的结构基础。
Nat Struct Mol Biol. 2018 Oct;25(10):981-987. doi: 10.1038/s41594-018-0137-2. Epub 2018 Oct 5.
7
gene mutation causing Distal Hereditary Motor Neuropathy in a Portuguese family.一个葡萄牙家族中导致远端遗传性运动神经病的基因突变。
Acta Myol. 2018 May 1;37(1):2-4. eCollection 2018 May.
8
Sigma 1 receptor: A novel therapeutic target in retinal disease.西格玛1受体：视网膜疾病中的新型治疗靶点。
Prog Retin Eye Res. 2018 Nov;67:130-149. doi: 10.1016/j.preteyeres.2018.07.003. Epub 2018 Aug 1.
9
Cocaine Blocks Effects of Hunger Hormone, Ghrelin, Via Interaction with Neuronal Sigma-1 Receptors.可卡因通过与神经元 sigma-1 受体相互作用阻断饥饿激素 ghrelin 的作用。
Mol Neurobiol. 2019 Feb;56(2):1196-1210. doi: 10.1007/s12035-018-1140-7. Epub 2018 Jun 7.
10
Fenfluramine diminishes NMDA receptor-mediated seizures via its mixed activity at serotonin 5HT2A and type 1 sigma receptors.芬氟拉明通过其对5-羟色胺5HT2A受体和1型σ受体的混合作用来减轻NMDA受体介导的癫痫发作。
Oncotarget. 2018 May 4;9(34):23373-23389. doi: 10.18632/oncotarget.25169.
Zotero 插件