Published research to date related to the Sigma-1 protein (σ1R) has been conducted with compounds not developed by Advantx Pharmaceuticals Inc. Our therapeutic candidate ADV127 is the first truly selective, pharmaceutical-grade compound in development targeting the Sigma-1 receptor with a newly designed, clean molecule with unambiguous agonist activity, far superior in potency, selectivity, safety, and efficacy to all others tested to date.
RECENT SCIENTIFIC PUBLICATIONS RELATED TO THE SIGMA-1 PROTEIN
N, N-Dimethyltryptamine, a natural hallucinogen, ameliorates Alzheimer’s disease by restoring neuronal Sigma-1 receptor-mediated endoplasmic reticulum-mitochondria crosstalk
By Dan Cheng, Zhuo-Gui Lei, Kin Chu, Oi Jin Honey Lam, Chun Yuan Chiang, and Zhang-Jin Zhang Excerpt from the article published in Alzheimer’s Research & Therapy volume 16, 95, 01 May 2024, DOI: https://doi.org/10.1186/s13195-024-01462-3 Abstract Background Aberrant neuronal Sigma-1 receptor (Sig-1r)-mediated endoplasmic reticulum (ER)- mitochondria signaling plays a key role in the neuronal cytopathology […]
Deletion of Sigmar1 leads to increased arterial stiffness and altered mitochondrial respiration resulting in vascular dysfunction
By Remex Naznin Sultana , Abdullah Chowdhury S. , Aishwarya Richa , Kolluru Gopi K. , Traylor James , Bhuiyan Mohammad Alfrad Nobel , Kevil Christopher G. , Orr A. Wayne , Rom Oren , Pattillo Christopher B. , and Bhuiyan Md. Shenuarin Excerpt of the article published in Frontiers in Physiology, 15, 29 April […]
Activation of σ-1 receptor mitigates estrogen withdrawal-induced anxiety/depressive-like behavior in mice via restoration of GABA/glutamate signaling and neuroplasticity in the hippocampus
By Peng Ren, Jing-Ya Wang, Hong-Lei Chen, Yue Wang, Lin-Yu Cui, Jing-Yao Duan, Wen-Zhi Guo, Yong-Qi Zhao, and Yun-Feng Li Excerpt from the article published in Journal of Pharmacological Sciences, Volume 154, Issue 4, April 2024, Pages 236-245, ISSN 1347-8613, DOI: https://doi.org/10.1016/j.jphs.2024.02.003. Abstract Postpartum depression (PPD) is a significant contributor to maternal morbidity and mortality. […]
Single cocaine exposure attenuates the intrinsic excitability of CRH neurons in the ventral BNST via Sigma-1 receptors
By Jintao Wu and Yue Zhao Excerpt from the article published in Translational Neuroscience, vol. 15, no. 1, April 24, 2024, pp. 20220339. DOI: https://doi.org/10.1515/tnsci-2022-0339 Abstract The ventral bed nucleus of the stria terminalis (vBNST) plays a key role in cocaine addiction, especially relapse. However, the direct effects of cocaine on corticotropin-releasing hormone (CRH) neurons […]
Benzomorphan and non-benzomorphan agonists differentially alter sigma-1 receptor quaternary structure, as does types of cellular stress
By Simon Couly, Yuko Yasui, Semnyonga Foncham, Ioannis Grammatikakis, Ashish Lal, Lei Shi, and Tsung-Ping Su Excerpt from the article published in Cellular and Molecular Life Sciences, Article 81, 14 (2024). Published 09 January 2024. DOI: https://doi.org/10.1007/s00018-023-05023-z Editor’s Highlights Abstract Sigma-1 receptor (S1R) is a calcium-sensitive, ligand-operated receptor chaperone present on the endoplasmic reticulum (ER) membrane. […]
Fluvoxamine Exerts Sigma-1R to Rescue Autophagy via Pom121-Mediated Nucleocytoplasmic Transport of TFEB
By Chun-Yu Lin, Hsiang-En Wu, Eddie Feng-Ju Weng, Hsuan-Cheng Wu, Tsung-Ping Su, and Shao-Ming Wang Excerpt from the article published in Molecular Neurobioligy (2024). 05 January 2024. DOI: https://doi.org/10.1007/s12035-023-03885-9 Editor’s Highlights Abstract Expansion of the GGGGCC-RNA repeat is a known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which currently have no cure. Recent […]
The Protective Role of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Protein Sigma-1 Receptor in Regulating Endothelial Inflammation and Permeability Associated with Acute Lung Injury
By Zahra Mahamed, Mohammad Shadab, Rauf Ahmad Najar, Michelle Warren Millar, Jashandeep Bal, Traci Pressley, and Fabeha Fazal Excerpt from the article published in Cells. 2024; 13(1):5. 19 December 2023, DOI: https://doi.org/10.3390/cells13010005 Editor’s Highlights Abstract Earlier studies from our lab identified endoplasmic reticulum (ER) chaperone BiP/GRP78, an important component of MAM, to be a novel determinant […]
Sigma-1 receptor activation mediates the sustained antidepressant effect of ketamine in mice via increasing BDNF levels
By Hui Ma, Jin-feng Li, Xin Qiao, Yue Zhang, Xiao-juan Hou, Hai-xia Chang, Hong-lei Chen, Yong Zhang, and Yun-feng Li Excerpt from the article published in Acta Pharmacologica Sinica 45, 704–713 (2024). DOI: https://doi.org/10.1038/s41401-023-01201-8 Abstract Sigma-1 receptor (S1R) is a unique multi-tasking chaperone protein in the endoplasmic reticulum. Since S1R agonists exhibit potent antidepressant-like activity, […]
Gut microbiota-derived short-chain fatty acids ameliorate methamphetamine-induced depression- and anxiety-like behaviors in a Sigmar-1 receptor-dependent manner
By Kaikai Zhang, Lijian Chen, Jianzheng Yang, Jiali Liu, Jiahao Li, Yi Liu, Xiuwen Li, Long Chen, Clare Hsu, Jiahao Zeng, Xiaoli Xie, and Qi Wanga Excerpt from the article published in Acta Pharm Sin B. 2023 Dec;13(12):4801-4822. Epub 2023 Sep 21. PMID: 38045052; PMCID: PMC10692394. DOI: 10.1016/j.apsb.2023.09.010 Editor’s Highlights Abstract Methamphetamine (Meth) abuse can […]
Sigma receptor ligands are potent anti-prion compounds that act independently of sigma receptor binding
By Robert C. C. Mercer, Nhat T. T. Le, Mei C. Q. Houser, Aaron B. Beeler, and David A. Harris Excerpt from the article published in bioRxiv 2023.11.28.569035; November 29, 2023. DOI: https://doi.org/10.1101/2023.11.28.569035 Editor’s Highlights Abstract Prion diseases are invariably fatal neurodegenerative diseases of humans and other animals for which there are no treatment options. Previous work from […]
Sigma-1 receptor agonism exacerbates immune-driven nociception: Role of TRPV1 + nociceptors
By M. Carmen Ruiz-Cantero, Miguel Á. Huerta, Miguel Á. Tejada, Miriam Santos-Caballero, Eduardo Fernández-Segura, Francisco J. Cañizares, José M. Entrena, José M. Baeyens, and Enrique J. Cobos Excerpt from the article published in Biomedicine & Pharmacotherapy, Volume 167, November 2023,115534, ISSN 0753-3322, DOI: https://doi.org/10.1016/j.biopha.2023.115534. Highlights Abstract The analgesic effects of sigma-1 antagonists are undisputed, but the effects […]
Mitochondria-associated membrane collapse impairs TBK1-mediated proteostatic stress response in ALS
By Seiji Watanabe, Yuri Murata, Yasuyoshi Oka, and Koji Yamanaka Excerpt from the article published in Proceedings of the National Academy of Sciences, November 15, 2023, 120 (47) e2315347120, DOI: https://doi.org/10.1073/pnas.2315347120 Editor’s Highlights Significance Recent studies, including ours, have suggested that mitochondria-associated membrane (MAM) disruption is a common pathogenic mechanism in amyotrophic lateral sclerosis (ALS). In the […]
A Practical Guide to Sigma-1 Receptor Positron Emission Tomography/Magnetic Resonance Imaging: A New Clinical Molecular Imaging Method to Identify Peripheral Pain Generators in Patients with Chronic Pain
By Bin Shen, Daehyun Yoon, Jessa Castillo, and Sandip Biswal Excerpt from the article published in Semin Musculoskelet Radiol, November 2023; 27(06): 601-617 DOI: 10.1055/s-0043-1775744 Editor’s Highlights Abstract Accurately identifying the peripheral pain generator in patients with chronic pain remains a major challenge for modern medicine. Millions of patients around the world suffer endlessly from […]
Sigma-1 Receptor Inhibition Reduces Mechanical Allodynia and Modulate Neuroinflammation in Chronic Neuropathic Pain
By Simona Denaro, Lorella Pasquinucci, Rita Turnaturi, Cristiana Alberghina, Lucia Longhitano, Sebastiano Giallongo, Giuliana Costanzo, Salvatore Spoto, Margherita Grasso, Agata Zappalà, Giovanni Li Volti, Daniele Tibullo, Nunzio Vicario, Rosalba Parenti, and Carmela Parenti Excerpt from the article published in Mol Neurobiol (November 3, 2023). DOI: https://doi.org/10.1007/s12035-023-03717-w Editor’s Highlights Abstract Neuropathic pain is one of the most […]
Sigma1 Regulates Lipid Droplet–Mediated Redox Homeostasis Required for Prostate Cancer Proliferation
By Halley M. Oyer; Alexandra R. Steck; Charles G. Longen; Sanjana Venkat; Konuralp Bayrak; Eleanor B. Munger; Dan Fu; Paola A. Castagnino; Christina M. Sanders; Nathalia A. Tancler; My T. Mai; Justin P. Myers; Matthew J. Schiewer; Nan Chen; Elahe A. Mostaghel; and Felix J. Kim Excerpt from the article published in Cancer Research Communications (October […]
Multi-Omics Analysis Reveals the Role of Sigma-1 Receptor in a Takotsubo-like Cardiomyopathy Model
By Yi Liu, Qing Chen, Jian-Zheng Yang, Xiu-Wen Li, Li-Jian Chen, Kai-Kai Zhang, Jia-Li Liu, Jia-Hao Li, Clare Hsu, Long Chen, Jia-Hao Zeng, Qi Wang, Dong Zhao, and Jing-Tao Xu Excerpt from the article published in Biomedicines. 12 October 2023; 11(10):2766. DOI: https://doi.org/10.3390/biomedicines11102766 Editor’s Highlights Abstract Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy that presents […]
Genetic and Pharmacological Blockade of Sigma-1 Receptors Attenuates Inflammation-Associated Hypersensitivity during Acute Colitis in CD1 Mice
By Sergio López-Estévez, Mònica Aguilera, Georgia Gris, Beatriz de la Puente, Alicia Carceller, and Vicente Martínez Excerpt from the article published in Biomedicines. 12 October 2023; 11(10):2758. DOI: https://doi.org/10.3390/biomedicines11102758 Editor’s Highlights Abstract Sigma-1 receptors (σ1Rs) are implicated in nociception, including pain sensitization, and inflammation. We assessed the role of σ1Rs on acute colitis-associated hypersensitivity using […]
Sigma-1 receptor agonism exacerbates immune-driven nociception: Role of TRPV1 + nociceptors
By M. Carmen Ruiz-Cantero, Miguel Á. Huerta, Miguel Á. Tejada, Miriam Santos-Caballero, Eduardo Fernández-Segura, Francisco J. Cañizares, José M. Entrena, José M. Baeyens, and Enrique J. Cobos Excerpt from the article published in Biomedicine & Pharmacotherapy, Volume 167, November 2023, 115534, ISSN 0753-3322, DOI: https://doi.org/10.1016/j.biopha.2023.115534. Highlights Abstract The analgesic effects of sigma-1 antagonists are undisputed, but the […]
Sigma Receptors: Novel Regulators of Iron/Heme Homeostasis and Ferroptosis
By Nhi T. Nguyen, Valeria Jaramillo-Martinez, Marilyn Mathew, Varshini V. Suresh, Sathish Sivaprakasam, Yangzom D. Bhutia, and Vadivel Ganapathy Excerpt from the article published in International Journal of Molecular Sciences. 28 September 2023; 24(19):14672. DOI: https://doi.org/10.3390/ijms241914672 Editor’s Higlights Abstract Sigma receptors are non-opiate/non-phencyclidine receptors that bind progesterone and/or heme and also several unrelated xenobiotics/chemicals. They […]
The Neuroprotective Effect of Activation of Sigma-1 Receptor on Neural Injury by Optic Nerve Crush
By Yao Chen; Xueli Yang; and Junfeng Mao Excerpt from the article published in Investigative Ophthalmology & Visual Science September 2023, Vol.64, 9. Doi:https://doi.org/10.1167/iovs.64.12.9 Editor’s Highlights Abstract Purpose: This study aimed to explore the neuroprotective effects of sigma-1 receptor (S1R) on optic nerve crush (ONC) mice by upregulating its expression through intravitreal injection of adeno-associated virus (AAV). […]
Sigma-1 receptor expression in a subpopulation of lumbar spinal cord microglia in response to peripheral nerve injury
By Ethan Schonfeld, Thomas Michael Johnstone, Ghani Haider, Aaryan Shah, Neelan Joseph Marianayagam, Sandip Biswal, and Anand Veeravagu Excerpt from the article published in Scientific Reports 13, 14762 (07 September 2023). DOI: https://doi.org/10.1038/s41598-023-42063-8 Editor’s Highlights Abstract Sigma-1 Receptor has been shown to localize to sites of peripheral nerve injury and back pain. Radioligand probes have been […]
Sigma-1 receptor knockout disturbs gut microbiota, remodels serum metabolome, and exacerbates isoprenaline-induced heart failure
By Jian-Zheng Yang, Kai-Kai Zhang, Hong-Wu Shen, Yi Liu, Xiu-Wen Li, Li-Jian Chen, Jia-Li Liu, Jia-Hao Li, Dong Zhao, Qi Wang, and Chu-Song Zhou Excerpt from the article published in Frontiers Microbiology, 31 August 2023, Sec. Microorganisms in Vertebrate Digestive Systems, Volume 14 – 2023, DOI: https://doi.org/10.3389/fmicb.2023.1255971 Editor’s Highlights Abstract Introduction: Heart failure (HF) is usually the […]
Structure-Based Modeling of Sigma 1 Receptor Interactions with Ligands and Cholesterol and Implications for Its Biological Function
By Meewhi Kim and Ilya Bezprozvanny Excerpt from the article published in International Journal of Molecular Sciences 24, no. 16: 12980. 19 August 2023, DOI: https://doi.org/10.3390/ijms241612980 Abstract The sigma 1 receptor (S1R) is a 223-amino-acid-long transmembrane endoplasmic reticulum (ER) protein. The S1R plays an important role in neuronal health and it is an established therapeutic target […]
The Sigma-1 Receptor Is a Novel Target for Improving Cold Preservation in Rodent Kidney Transplants
By Adam Hosszu, Akos R. Toth, Tamas Lakat, Ganna Stepanova, Zsuzsanna Antal, Laszlo J. Wagner, Attila J. Szabo, and Andrea Fekete Excerpt from the article published in International Journal of Molecular Sciences. 19 July 2023; 24(14):11630. https://doi.org/10.3390/ijms241411630 Editor’s highlights Abstract Kidney transplantation is the preferred treatment for patients with end-stage kidney disease. Maintaining organ viability […]
An Emerging Role for Sigma Receptor 1 in Personalized Treatment of Breast Cancer
By Taylor S. Robinson and Mahasin A. Osman Excerpt from the article published in Cancers, 2 July 2023, 15, 3464. DOI: https://doi.org/10.3390/cancers15133464 Editor’s Highlights Simple Summary Breast cancer continues to be the number one cause of cancer mortality among women. Because breast cancer is a heterogenous disease there is a need for a more personalized approach to […]
Novel compound inhibits glycolysis, proteotoxicity, inflammation, and impairments in animal models of Alzheimer’s, Huntington’s, and stroke: Aging as a consequence of glycolysis
By Rachel Litke, Kun-Hyung Roh, Yonejung Yoon, Sindhu Vangeti, Irene Ramos-lopez, Husnu Kaniskan, Jian Jin, Christopher Kellner, and Charles Mobbs Excerpt from the article published in bioRxiv 2023.06.12, 544352; doi: https://doi.org/10.1101/2023.06.12.544352 Editor’s Highlights Abstract Alzheimer’s Disease (AD) and other age-related diseases are increasingly among the most devastating strains on public health systems as the population ages, yet […]
Defining the ligand-dependent proximatome of the sigma 1 receptor
By Jing Zhao, Rajalakshmi Veeranan-Karmegam, Frederick C. Baker, Barbara A. Mysona, Pritha Bagchi, Yutao Liu, Sylvia B. Smith, Graydon B. Gonsalvez, and Kathryn E. Bollinger Excerpt from the article published in Frontiers in Cell and Developmental Biology, 11, 07 June 2023Sec. Membrane Traffic, DOI: 1045759.https://doi.org/10.3389/fcell.2023.1045759 Editor’s Highlights Abstract Sigma 1 Receptor (S1R) is a therapeutic target for a […]
Targeting Sigma-1 Receptor: A Promising Strategy in the Treatment of Parkinson’s Disease
By Talha Siddiqui and Lokesh Kumar Bhatt Excerpt from the article published in Neurochem Research. 31 May 2023. DOI: https://doi.org/10.1007/s11064-023-03960-6 Editor’s Highlights Abstract Parkinson’s disease is a neurodegenerative disease affecting mainly the elderly population. It is characterized by the loss of dopaminergic neurons of the substantia nigra pars compacta region. Parkinson’s disease patients exhibit motor […]
Sig1R activates extracellular matrix-induced bladder cancer cell proliferation and angiogenesis by combing β-integrin
By Feng Zhao, Tianli Yang, Liuhua Zhou, Rongfei Li, Jingyu Liu, Jun Zhao, and Ruipeng Jia Excerpt from the article published in Aging (Albany NY). 2023 May 16; DOI: https://doi.org/10.18632/aging.204721 Editor’s Highlights Abstract The extracellular matrix (ECM) regulates many biological functions involved in tumorigenesis and tumor development; however, the underlying mechanism remains unknown. Sigma 1 […]
Sigma-1 receptor and seizures
By Edijs Vavers, Liga Zvejniece, and Maija Dambrova Excerpt from the article published in Pharmacological Research, Volume 191, May 2023, 106771, ISSN 1043-6618, DOI: https://doi.org/10.1016/j.phrs.2023.106771. Editor’s Highlights Abstract Over the last decade, sigma-1 receptor (Sig1R) has been recognized as a valid target for the treatment of seizure disorders and seizure-related comorbidities. Clinical trials with Sig1R […]
SIGMAR1 Confers Innate Resilience against Neurodegeneration
By Simon Couly, Yuko Yasui, and Tsung-Ping Su Excerpt from the article published in the International Journal of Molecular Sciences 24, no. 9: 7767. 24 April 2023, DOI: https://doi.org/10.3390/ijms24097767 Abstract The sigma-1 receptor (SIGMAR1) is one of a kind: a receptor chaperone protein. This 223 amino acid-long protein is enriched at the mitochondria-associated endoplasmic reticulum membrane […]
Gut microbiota from sigma-1 receptor knockout mice induces depression-like behaviors and modulates the cAMP/CREB/BDNF signaling pathway
By Jia-Hao Li, Jia-Li Liu, Xiu-Wen Li, Yi Liu, Jian-Zheng Yang, Li-Jian Chen, Kai-Kai Zhang, Xiao-Li Xie, and Qi Wang Excerpt from the article published in Frontiers in Microbiology, 06 April 2023, Sec. Evolutionary and Genomic Microbiology, Volume 14 – 2023, DOI: https://doi.org/10.3389/fmicb.2023.1143648 Editor’s Highlights Abstract Introduction: Depression is a common mental disorder that affects approximately 350 […]
Early Alterations of RNA Binding Protein (RBP) Homeostasis and ER Stress-Mediated Autophagy Contributes to Progressive Retinal Degeneration in the rd10 Mouse Model of Retinitis Pigmentosa (RP)
By Alfred Yamoah, Priyanka Tripathi, Haihong Guo, Leonie Scheve, Peter Walter, Sandra Johnen, Frank Müller, Joachim Weis, and Anand Goswami Excerpt from the article published in Cells. 6 April 2023; 12(7):1094. DOI: https://doi.org/10.3390/cells12071094 Editor’s Highlights Abstract The retinal degeneration 10 (rd10) mouse model is widely used to study retinitis pigmentosa (RP) pathomechanisms. It offers a […]
Investigation of the Entry Pathway and Molecular Nature of σ1 Receptor Ligands
By Gianmarco Pascarella, Lorenzo Antonelli, Daniele Narzi, Theo Battista, Annarita Fiorillo, Gianni Colotti, Leonardo Guidoni, Veronica Morea, and Andrea Ilari Excerpt from the article published in the International Journal of Molecular Sciences. 24(7):6367. 28 March 2023. DOI: https://doi.org/10.3390/ijms24076367 Editor’s Highlights Abstract The σ1 receptor (σ1-R) is an enigmatic endoplasmic reticulum resident transmembrane protein implicated in […]
Sigmar1 ablation leads to lung pathological changes associated with pulmonary fibrosis, inflammation, and altered surfactant proteins levels
By Remex Naznin Sultana, Abdullah Chowdhury S., Aishwarya Richa, Nitu Sadia S., Traylor James, Hartman Brandon, King Judy, Bhuiyan Mohammad Alfrad Nobel, Kevil Christopher G., Orr A. Wayne, and Bhuiyan Md. Shenuarin Excerpt from the article published in Frontiers in Physiology, volume 14, 27 March 2023Sec. Respiratory Physiology and Pathophysiology, ISSN 1664-042X, DOI: 10.3389/fphys.2023.1118770 Editor’s […]
Sigma-1 receptor modulation fine-tunes KV1.5 channels and impacts pulmonary vascular function
By Alba Vera-Zambrano, Maria Baena-Nuevo, Susanne Rinné, Marta Villegas-Esguevillas, Bianca Barreira, Gokcen Telli, Angela de Benito-Bueno, José Antonio Blázquez, Belén Climent, Francisco Pérez-Vizcaino, Carmen Valenzuela, Niels Decher, Teresa Gonzalez, and Angel Cogolludo Excerpt from the article published in Pharmacological Research, Volume 189, March 2023, 106684,ISSN 1043-6618, DOI: https://doi.org/10.1016/j.phrs.2023.106684. Editor’s Highlights Abstract KV1.5 channels are key […]
Sphingoid Bases Regulate the Sigma-1 Receptor—Sphingosine and N,N’-Dimethylsphingosine Are Endogenous Agonists
By Jing Li, Kenneth A. Satyshur, Lian-Wang Guo, and Arnold E. Ruoho Excerpt from the article published in the International Journal of Molecular Sciences. 2023; 24(4):3103; 4 February 2023, DOI: https://doi.org/10.3390/ijms24043103 Editor’s Highlights Abstract Both bioactive sphingolipids and Sigma-1 receptor (S1R) chaperones occur ubiquitously in mammalian cell membranes. Endogenous compounds that regulate the S1R are […]
Sigma-1 receptor maintains ATAD3A as a monomer to inhibit mitochondrial fragmentation at the mitochondria-associated membrane in amyotrophic lateral sclerosis
By Seiji Watanabe, Mai Horiuchi, Yuri Murata, Okiru Komine, Noe Kawade, Akira Sobue, and Koji Yamanaka Excerpt from the article published in Neurobiology of Disease, 2 February 2023, 106031, ISSN 0969-9961, DOI: https://doi.org/10.1016/j.nbd.2023.106031 Editor’s Highlights Autors’ Highlights Abstract Organelle contact sites are multifunctional platforms for maintaining cellular homeostasis. Alternations of the mitochondria-associated membranes (MAM), one […]
TRPA1 modulation by Sigma-1 receptor prevents oxaliplatin-induced painful peripheral neuropathy
By Aida Marcotti, Jorge Fernández-Trillo, Alejandro González, Marta Vizcaíno-Escoto, Pablo Ros-Arlanzón, Luz Romero, José Miguel Vela, Ana Gomis, Félix Viana, and Elvira de la Peña Excerpt from the article published in Brain, Volume 146, Issue 2, February 2023, Pages 475–491, DOI: https://doi.org/10.1093/brain/awac273 Editor’s Highlights Abstract Chemotherapy-induced peripheral neuropathy is a frequent, disabling side effect of anticancer […]
Sigma-1 Receptor Signaling: In Search of New Therapeutic Alternatives for Cardiovascular and Renal Diseases
By Francisco Javier Munguia-Galaviz, Alejandra Guillermina Miranda-Diaz, Miguel Alejandro Cardenas-Sosa, and Raquel Echavarria Excerpt from the article published in the International Journal of Molecular Sciences. 19 January 2023; 24(3):1997. DOI: https://doi.org/10.3390/ijms24031997 Editor’s Hihghlights Abstract Cardiovascular and renal diseases are among the leading causes of death worldwide, and regardless of current efforts, there is a demanding […]
Overview of Sigma-1R Subcellular Specific Biological Functions and Role in Neuroprotection
By Véronik Lachance, Sara-Maude Bélanger, Célia Hay, Victoria Le Corvec, Vina Banouvong, Mathieu Lapalme, Khadija Tarmoun, Guillaume Beaucaire, Marc P. Lussier, and Saïd Kourrich Excerpt from the article published in the International Journal of Molecular Sciences. 19 January 2023; 24(3):1971. DOI: https://doi.org/10.3390/ijms24031971 Editor’s Highlights Abstract For the past several years, fundamental research on Sigma-1R (S1R) […]
Chaperone-Dependent Mechanisms as a Pharmacological Target for Neuroprotection
By Mikhail V. Voronin, Elena V. Abramova, Ekaterina R. Verbovaya, Yulia V. Vakhitova, and Sergei B. Seredenin Excerpt from the article published in International Journal of Molecular Sciences 24, no. 1: 823. 3 January 2023, DOI: https://doi.org/10.3390/ijms24010823 Editor’s Highlights Abstract Modern pharmacotherapy of neurodegenerative diseases is predominantly symptomatic and does not allow vicious circles causing disease […]
Sigma-1 Receptor Activation Improves Oligodendrogenesis and Promotes White-Matter Integrity after Stroke in Mice with Diabetic Mellitus
By Wenjing Song, Yang Yao, Heling Zhang, Xin Hao, Liping Zhou, Zhixiao Song, Tiantian Wei, Tianyan Chi, Peng Liu, Xuefei Ji, and Libo Zou Excerpt from the article published in Molecules 2023, 28(1), 390; 2 January 2023; DOI: https://doi.org/10.3390/molecules28010390 Editor’s Highlights Abstract Diabetes mellitus (DM) is a major risk factor for stroke and exacerbates white-matter damage in […]
Sigma-1 Receptor as a Protective Factor for Diabetes-Associated Cognitive Dysfunction via Regulating Astrocytic Endoplasmic Reticulum-Mitochondrion Contact and Endoplasmic Reticulum Stress
By Mengyu Du, Tao Jiang, Shuxuan He Bo Cheng, Xin Zhang, Liya Li, Lan Yang, Wei Gao, Yansong Li, and Qiang Wang Excerpt from the article published in Cells 2023, 12(1), 197; 3 January 2023, DOI: https://doi.org/10.3390/cells12010197 Editor’s Highlights Abstract The prevalence of diabetes-associated cognitive dysfunction (DACD) has increased to 13.5%. Dementia, as the most severe DACD, […]
Sigma-1 receptor-regulated efferocytosis by infiltrating circulating macrophages/microglial cells protects against neuronal impairments and promotes functional recovery in cerebral ischemic stroke
By Gufang Zhang, Qi Li, Weijie Tao, Pingping Qin, Jiali Chen, Huicui Yang, Jiaojiao Chen, Hua Liu, Qijun Dai, and Xuechu Zhen Excerpt from the article published in Theranostics. 2023 Jan 1;13(2):543-559. DOI: 10.7150/thno.77088. PMID: 36632219; PMCID: PMC9830433. Editor’s Highlights Abstract Background: Efferocytosis of apoptotic neurons by macrophages is essential for the resolution of inflammation and […]
αN-Acetyl β-Endorphin Is an Endogenous Ligand of σ1Rs That Regulates Mu-Opioid Receptor Signaling by Exchanging G Proteins for σ2Rs in σ1R Oligomers
By Javier Garzón-Niño, Elsa Cortés-Montero, María Rodríguez-Muñoz, and Pilar Sánchez-Blázquez Excerpt from the article published in the International Journal of Molecular Sciences. 2023; 24(1):582, 29 December 2022, DOI: https://doi.org/10.3390/ijms24010582 Editor’s Highlights Abstract The opioid peptide β-endorphin coexists in the pituitary and brain in its αN-acetylated form, which does not bind to opioid receptors. We now report […]
Sigma-1 receptor is involved in modification of ER-mitochondria proximity and Ca2+ homeostasis in cardiomyocytes
By Hideaki Tagashira, Md. Shenuarin Bhuiyan, Yasuharu Shinoda, Ichiro Kawahata, Tomohiro Numata, and Kohji Fukunaga Introduction to the article published in Journal of Pharmacological Sciences, December 10, 2022, ISSN 1347-8613, DOI: https://doi.org/10.1016/j.jphs.2022.12.005. Editor’s Highlights Abstract The Sigma-1 receptor (Sigmar1) is downregulated in heart failure model mice with mitochondrial dysfunction. However, the mechanism in detail has […]
Mitochondria in Huntington’s disease: implications in pathogenesis and mitochondrial-targeted therapeutic strategies
By Ana Maria Jurcau, and Carolina Maria Jurcau Excerpt from the article published in Neural Regeneration Research 18(7):p 1472-1477, July 2023. | DOI: 10.4103/1673-5374.360289 Editor’s Highlights Abstract Huntington’s disease is a genetic disease caused by expanded CAG repeats on exon 1 of the huntingtin gene located on chromosome 4. Compelling evidence implicates impaired mitochondrial energetics, […]
Retinal Photoreceptor Protection in an AMD-Related Mouse Model by Selective Sigma-1 or Sigma-2 Receptor Modulation
By Timur A. Mavlyutov, Jing Li, Xinying Liu, Hongtao Shen, Huan Yang, Christopher R. McCurdy, Bikash Pattnaik, and Lian-Wang Guo Excerpt from the article published in Genes 13(12):2386, 16 December 2022, DOI: https://doi.org/10.3390/genes13122386 Editor’s Highlights Abstract The structurally and genetically distinct sigma-1 receptor (S1R) and sigma-2 receptor (S2R) comprise a unique class of drug binding […]
The sigma-1 receptor curtails endogenous opioid analgesia during sensitization of TRPV1 nociceptors
By M. Carmen Ruiz-Cantero, Elsa Cortés-Montero, Aakanksha Jain, Ángeles Montilla-García, Inmaculada Bravo-Caparrós, Jaehoon Shim, Pilar Sánchez-Blázquez, Clifford J. Woolf, José M. Baeyens, and Enrique J. Cobos Excerpt from the article published in British Journal of Pharmacology, 1– 20, 07 December 2022, DOI: https://doi.org/10.1111/bph.16003 Editor’s Highlights Abstract Background and Purpose: Peripheral sensitization contributes to pathological pain. While prostaglandin […]
Protein Misfolding and Aggregation in the Brain: Common Pathogenetic Pathways in Neurodegenerative and Mental Disorders
By Aleksandra Ochneva, Yana Zorkina, Olga Abramova, Olga Pavlova, Valeriya Ushakova, Anna Morozova, Eugene Zubkov, Konstantin Pavlov, Olga Gurina, and Vladimir Chekhonin Excerpt from the article published in International Journal of Molecular Sciences 23, no. 22: 14498. 21 November 2022, DOI: https://doi.org/10.3390/ijms232214498 Editor’s Highlights Abstract Mental disorders represent common brain diseases characterized by substantial impairments of […]
Sigma-1 receptor agonist PRE-084 confers protection against TAR DNA-binding protein-43 toxicity through NRF2 signalling
By Christelle Lasbleiz, Amandine Peyrel, Pauline Tarot, Jérôme Sarniguet, Lucie Crouzier, Nicolas Cubedo, Benjamin Delprat, Mireille Rossel, Tangui Maurice, Jean-Charles Liévens Excerpt from the article published in Redox Biology, 17 November 2022, 102542, ISSN 2213-2317,DOI: https://doi.org/10.1016/j.redox.2022.102542. Editor’s Highlights Autors’ Highlights Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting upper and lower motor neurons. […]
The regulatory role of endoplasmic reticulum chaperone proteins in neurodevelopment
By Hongji Sun, Mengxue Wu, Minxin Wang, Xiaomin Zhang, and Jia Zhu Excerpt from the article published in Frontiers of Neuroscience, 15 November 2022, Sec. Neurodevelopment, DOI: https://doi.org/10.3389/fnins.2022.1032607 Editor’s Highlights Abstract The endoplasmic reticulum (ER) is the largest tubular reticular organelle spanning the cell. As the main site of protein synthesis, Ca2+ homeostasis maintenance and lipid […]
Sigma Antagonists for Treatment of Neuropathic Pain Syndromes in Cancer Patients: A Narrative Review
By Joseph V. Pergolizzi, Jr. and Jo Ann LeQuang Article published in Journal of Cancer Research Updates, 11, 70–77, 2022-10-27, DOI: https://doi.org/10.30683/1929-2279.2022.11.10 Abstract Almost 40% of cancer patients have neuropathic pain or mixed pain with a neuropathic component, which can be intense, debilitating, and challenging to treat. New studies on sigma receptors show these enigmatic ligand-binding […]
Safe and Efficient Sigma1 Ligand: A Potential Drug Candidate for Multiple Sclerosis
By Bénédicte Oxombre, Fahima Madouri, Anne-Sophie Journé, Séverine Ravez, Eloise Woitrain, Pascal Odou, Nathalie Duhal, Sandro Ninni, David Montaigne, Nadira Delhem, Patrick Vermersch, and Patricia Melnyk Excerpt from the article published in International Journal of Molecular Sciences 23, no. 19: 11893. 6 October 2022. DOI: https://doi.org/10.3390/ijms231911893 Editor’s Highlights In the last few decades, the sigma1 (S1R) […]
Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids
By Alba Vidal-Torres, Begoña Fernández-Pastor, Mónica García, Eva Ayet, Anna Cabot, Javier Burgueño, Xavier Monroy, Bertrand Aubel, Xavier Codony, Luz Romero, Rosalía Pascual, Maria Teresa Serafini, Gregorio Encina, Carmen Almansa, Daniel Zamanillo, Manuel Merlos, and José Miguel Vela Excerpt from the article published in Acta Pharmaceutica Sinica B, September 25, 2022, ISSN 2211-3835, DOI: https://doi.org/10.1016/j.apsb.2022.09.018 […]
Specific detection and deletion of the sigma-1 receptor widely expressed in neurons and glial cells in vivo
By Qing Liu, Qilin Guo, Li-Pao Fang, Honghong Yao, Anja Scheller, Frank Kirchhoff, and Wenhui Huang Excerpt from the article published in Journal of Neurochemistry, 00, 1– 22, 09 September 2022, DOI: https://doi.org/10.1111/jnc.15693 Editor’s Highlights Abstract The chaperon protein sigma-1 receptor (S1R) has been discovered over 40 years ago. Recent pharmacological studies using S1R exogenous ligands demonstrated a promising […]
The Adhesion GPCR VLGR1/ADGRV1 Regulates the Ca2+ Homeostasis at Mitochondria-Associated ER Membranes
By Jacek Krzysko, Filip Maciag, Anna Mertens, Baran Enes Güler, Joshua Linnert, Karsten Boldt, Marius Ueffing, Kerstin Nagel-Wolfrum, Martin Heine, and Uwe Wolfrum Excerpt from the article published in Cells. 2022; 11(18):2790. 7 September 2022. DOI: https://doi.org/10.3390/cells11182790 Editor’s Highlights The VLGR1 (very large G protein-coupled receptor-1), also known as ADGRV1, GPR98, and MASS, is the […]
Defining the Ligand-dependent Interactome of the Sigma 1 Receptor
By Jing Zhao, Rajalakshmi Veeranan-Karmegam, Frederick C. Baker, Barbara A. Mysona, Pritha Bagchi, Yutao Liu, Sylvia B. Smith, Graydon B. Gonsalvez, and Kathryn E. Bollinger Excerpt from the article published in bioRxiv 2022.06.22.497210; Published June 25, 2022, DOI: https://doi.org/10.1101/2022.06.22.497210 Editor’s Highlights The sigma 1 receptor (S1R) is a therapeutic target for a wide spectrum of pathological conditions. S1R has […]
Dysregulated Ca2+ Homeostasis as a Central Theme in Neurodegeneration: Lessons from Alzheimer’s Disease and Wolfram Syndrome
By Manon Callens, Jens Loncke, and Geert Bultynck Excerpt from the article published in Cells 2022, 11, 1963. DOI: https://doi.org/10.3390/cells11121963 Editor’s Highlights Abstract Calcium ions (Ca2+) operate as important messengers in the cell, indispensable for signaling the underlying numerous cellular processes in all of the cell types in the human body. In neurons, Ca2+ signaling is crucial for […]
A Non-Canonical Role for IRE1α Links ER and Mitochondria as Key Regulators of Astrocyte Dysfunction: Implications in Methamphetamine use and HIV-Associated Neurocognitive Disorders
By Jessica Proulx, Satomi Stacy, In-Woo Park, and Kathleen Borgmann Excerpt from the article published in Frontiers in Neuroscience, 16, 17 June 2022, DOI https://doi.org/10.3389/fnins.2022.906651 Editor’s Highlights During human immunodeficiency virus (HIV)-1 infection or (METH)amphetamine exposure, astrocytes shift their neuroprotective functions and can become neurotoxic. As common comorbidity among HIV-1 infected individuals (METH)amphetamine use can […]
Sigma-1 Receptors in Depression: Mechanism and Therapeutic Development
By Peng Ren, Jingya Wang, Nanxi Li, Guangxiang Li, Hui Ma, Yongqi Zhao, and Yunfeng Li Excerpt from the article published in Frontiers on Pharmacology, 16 June 2022, Sec.Neuropharmacology, DOI: https://doi.org/10.3389/fphar.2022.925879 Editor’s Highlights Depression is a mainly persistent mood disorder that negatively impacts the social, vocational and educational aspects of people’s life. Sigma-1 receptors are […]
Molecular function of Sigma-1 receptor in obesity-induced metabolic dysfunction
By Chowdhury S. Abdullah, Shafiul Alam, Richa Aishwarya, Jonette M. Green, A. Wayne Orr, Matthew D. Woolard, Aimee E. Vozelinek, Norman R. Harris, Randa S. Eshaq, Christopher G. Kevil, and Shenuarin Bhuiyan Introduction to the article published in Journal of Molecular and Cellular Cardiology, 046| VOLUME 112, P149, NOVEMBER 01, 2017, DOI: https://doi.org/10.1016/j.yjmcc.2017.07.058 Editor’s Highlights Sigma-1 receptor (Sigmar1) […]
Sigma-1 receptor attenuates osteoclastogenesis by promoting ER-associated degradation of SERCA2
By Xiaoan Wei, Zeyu Zheng, Zhenhua Feng, Lin Zheng, Siyue Tao, Bingjie Zheng, Bao Huang, Xuyang Zhang, Junhui Liu, Yilei Chen, Wentian Zong, Zhi Shan, Shunwu Fan, Jian Chen, and Fengdong Zhao Excerpt from the article published in EMBO Molecular Medicine e15373 25 May 2022 DOI: https://doi.org/10.15252/emmm.202115373 Editor’s Highlights Abstract Sigma-1 receptor (Sigmar1) is a […]
Mitochondrial transfer/transplantation: an emerging therapeutic approach for multiple diseases
By Zonghan Liu, Yi Sun, Zhengtang Qi, Lu Cao, and Shuzhe Ding Excerpt from the article published in Cell and Bioscience 12, 66 (2022). Published: 19 May 2022, DOI: https://doi.org/10.1186/s13578-022-00805-7 Editor’s Highlights Mitochondria are semiautonomous, semiself-replicating, highly dynamic organelles, endowed with their own circular, double-stranded DNA molecule that spans 16.6 kb and intramitochondrial replication and translational machinery. Intercellular mitochondrial […]
Intracellular dynamics of the Sigma-1 receptor observed with super-resolution imaging microscopy
By Sergei Kopanchuk, Edijs Vavers , Santa Veiksina, Kadri Ligi, Liga Zvejniece, Maija Dambrova, and Ago Rinken Excerpt from the article published in PLoS ONE 17(5): e0268563. May 18, 2022, DOI: https://doi.org/10.1371/journal.pone.0268563 Editor’s Highlights The sigma-1 receptor (Sig1R) has been described as an intracellular protein modulator, a chaperone protein that localizes in the endoplasmic reticulum […]
Cellular interorganelle crosstalk in health and disease states: A glimpse on nephrology-related conditions
By Fateme Shamekhi Amiri Excerpt from the article published in Archives of Clinical Nephrology 8(1): 007-027. DOI: 10.17352/acn.000059 Editor’s Highlights Mitochondria as a signalling organelle associates with the cellular signalling environment and mediates gene expression programs. Mitochondria are constantly interacting with other organelles through signalling pathways, and on some occasions even though physical contact sites. Sigma-1receptor […]
Chronic Sigma 1 receptor activation alleviates right ventricular dysfunction secondary to pulmonary arterial hypertension
By Yazhou Sun, Weiguo Wan, Xin Zhao, Xueyu Han, Tianxin Ye, Xiaoli Chen, Qian Ran, Xiukun Wang, Xin Liu, Chuan Qu, Shaobo Shi, Cui Zhang & Bo Yang (2022) Excerpt from the article published in Bioengineered, 13:4, 10843-10856, DOI: 10.1080/21655979.2022.2065953 Editor’s Highlights Pulmonary arterial hypertension (PAH) is a chronic disease characterized by a progressive elevation in mean pulmonary artery pressure, which […]
Effects of sub-chronic, in vivo administration of sigma non-opioid intracellular receptor 1 ligands on platelet and aortic arachidonate cascade in rats
By Sándor Váczi, Lilla Barna, Krisztián Laczi, Ferenc Tömösi, Gábor Rákhely, Botond Penke, Lívia Fülöp, Ferenc Bogár, Tamás Janáky, Mária A. Deli, and Zsófia Mezei Excerpt from the article published in European Journal of Pharmacology, 2022, 174983 Doi: https://doi.org/10.1016/j.ejphar.2022.174983. Editor’s Highlights Only a fraction of all cardiovascular diseases is of cardiac origin, and macro-and microvascular […]
Activation of Sigma-1 Receptor Alleviates ER-Associated Cell Death and Microglia Activation in Traumatically Injured Mice
By Mingming Shi, Liang Liu, Xiaobin Min, Liang Mi, Yan Chai, Fanglian Chen, Jianhao Wang, Shuyuan Yue, Jianning Zhang, Quanjun Deng, and Xin Chen Excerpt from the article published in Journal of Clinical Medicine 2022, 11, 2348 Doi: https://doi.org/10.3390/jcm11092348 Editor’s Highlights The sigma-1 receptor (Sig-1R) is a ubiquitous ER-resident chaperone localized acting as a dynamic pluripotent […]
Sigma‑1 receptor overexpression promotes proliferation and ameliorates cell apoptosis in β‑cells
By Mengting Ke, Fengping Lin, Huawei Wang, Guangzhen He, Jieyuan Feng, Linyang Song, Yancheng Xu, and Jie Liu Excerpt from the article published in Molecular Medicine Reports 25, no. 5 (2022): 170. https://doi.org/10.3892/mmr.2022.12686 Editor’s Highlights Sigma-1 receptor (Sig-1R) is a class of receptors that serve unique physiological functions due to the lack of homology with […]
Order through destruction: how ER-associated protein degradation contributes to organelle homeostasis
By John C Christianson and Pedro Carvalho Excerpt from the article published in The EMBO Journal (2022)41:e109845 DOI: https://doi.org/10.15252/embj.2021109845 Editor’s Highlights As a large, multifunctional organelle, the endoplasmic reticulum (ER) houses robust protein quality control systems, on which it relies heavily. The best-characterized protein quality control system of the ER is the ubiquitin-proteasome-dependent process of […]
An open-like conformation of the sigma-1 receptor reveals its ligand entry pathway
By Meng, F., Xiao, Y., Ji, Y. et al. Excerpt from the article published in Nat Commun 13, 1267 (2022). https://doi.org/10.1038/s41467-022-28946-w Editor’s Highlights Data suggest that access to the σ1R ligand binding site is likely achieved by protein conformational changes that involve the carboxy-terminal two-helix bundle, rather than structural changes in the cupin-fold domain. The PATH2 access hypothesis […]
Long COVID, neuropsychiatric disorders, psychotropics, present and future
By Siu Wa Tang, Brian E. Leonard, and Daiga Maret Helmeste Excerpt from the article published in Acta Neuropsychiatrica, 34(3), 109-126. DOI: 10.1017/neu.2022.6 Editor’s Highlights The term Long COVID is used to refer to the lingering or protracted illness, from 4 to 12 weeks after the acute illness and during recovery. Long-term psychological or adverse mental […]
Sigma 1 Receptor Contributes to Astrocyte-Mediated Retinal Ganglion Cell Protection
By Jing Zhao; Graydon B. Gonsalvez; Barbara A. Mysona; Sylvia B. Smith; Kathryn E. Bollinger Excerpt from the article published in Investigative Ophthalmology & Visual Science February 2022, Vol.63, 1. doi:https://doi.org/10.1167/iovs.63.2.1 Editor’s Highlights Abstract Purpose: Sigma 1 receptor (S1R) is expressed in retinal ganglion cells (RGCs) and astrocytes, and its activation is neuroprotective. We evaluated the contribution of S1R within optic […]
Novel Therapeutic Target for Prevention of Neurodegenerative Diseases: Modulation of Neuroinflammation with Sig-1R Ligands
By Ferenc Bogár, Lívia Fül. and Botond Penke Excerpt from the article published in Biomolecules 2022, 12, 363, Published: 25 February 2022, DOI: https://doi.org/10.3390/biom12030363 Editor’s Highlights Sigma-1 Receptor is a Central Regulator of Cell Survival As Sig-1R controls ER stress and the inflammatory processes in the cells, Sig-1R agonists have been tested in preclinical studies and […]
Impact of Two Neuronal Sigma‐1 Receptor Modulators, PRE084 and DMT, on Neurogenesis and Neuroinflammation in an Aβ1‐42‐Injected, Wild‐Type Mouse Model of AD
By Emőke Borbély, Viktória Varga, Titanilla Szögi, Ildikó Schuster, Zsolt Bozsó, Botond Penke and Lívia Fülöp Excerpt from the article published in Int. J. Mol. Sci. 2022, 23, 2514. https://doi.org/10.3390/ijms23052514 Editor’s Highlights Adult neurogenesis is essential for CNS plasticity. In early AD, neurogenic impairment can be observed, accompanied by hyperreactive astrogliosis. The highly selective S1R […]
Sigma non-opioid receptor 1 is a potential therapeutic target for long QT syndrome
by Song, L., Bekdash, R., Morikawa, K. et al. Excerpt from the article published in Nat Cardiovasc Res 1, 142–156 (2022). https://doi.org/10.1038/s44161-021-00016-2 Editor’s Highlights Mutations in the CACNA1C gene, encoding the α2δ-1 subunit in the calcium channel CaV1.2, cause a life-threatening form of long QT syndrome (LQTS) named Timothy syndrome. SIGMA-1 receptor could be a therapeutic target for TS and […]
The molecular role of Sigmar1 in regulating mitochondrial function through mitochondrial localization in cardiomyocytes
by Chowdhury S. Abdullah, Richa Aishwarya, Shafiul Alam, Naznin Sultana Remex, Mahboob Morshed, Sadia Nitu, Sumitra Miriyala, Manikandan Panchatcharam, Brandon Hartman, Judy King, Mohammad Alfrad Nobel Bhuiyan, James Traylor, Christopher G. Kevil, A. Wayne Orr, Md. Shenuarin Bhuiyan Excerpt from the article published in Mitochondrion, Volume 62, 2022, Pages 159-175, ISSN 1567-7249, https://doi.org/10.1016/j.mito.2021.12.002. Editor’s Highlights […]
Sigma-1 Receptor is a Pharmacological Target to Promote Neuroprotection in the SOD1G93A ALS Mice
By Núria Gaja-Capdevila, Neus Hernández, Xavier Navarro, and Mireia Herrando-Grabulosa Excerpt from the article published in Frontiers in Pharmacology, 10 December 2021 | https://doi.org/10.3389/fphar.2021.780588 Editor’s Highlights Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive loss of upper and lower motoneurons (MNs), causing muscle paralysis and early death. The etiology underlying the […]
Superoxide dismutase and the sigma1 receptor as key elements of the antioxidant system in human gastrointestinal tract cancers
By Michał Skrzycki Excerpt from the article published in Open Life Sciences, vol. 16, no. 1, 2021, pp. 1225-1239. https://doi.org/10.1515/biol-2021-0124 Editor’s Highlights The Sigma-1 receptor (Sig1R) is a membrane and cytosol protein with a sequence similar to fungal C-8.7 sterol isomerase but without any other known homology with other mammalian proteins. The Sig1R is most often […]
The Sigma-1 receptor is an ER-localized type II membrane protein
By Neeraj Sharma, Chaitanya Patel, Marina Shenkman, Amit Kessel, Nir Ben-Tal, Gerardo Z. Lederkremer Excerpt from the article published in Journal of Biological Chemistry, 297, 5, 101299, November 2021 DOI: https://doi.org/10.1016/j.jbc.2021.101299 Editor’s Highlights The Sigma-1 receptor (S1R) is a small transmembrane protein (25 KDa), which is localized predominantly in the endoplasmic reticulum (ER), preferentially at the […]
Revisiting the sigma-1 receptor as a biological target to treat affective and cognitive disorders
by Kinga Sałaciak, Karolina Pytka Excerpt from the article published in Neuroscience & Biobehavioral Reviews Volume 132, January 2022, ISSN 0149-7634, https://doi.org/10.1016/j.neubiorev.2021.10.037. Editor’s Highlights Sigma-1 receptors are unique therapeutic targets modulating the activity of various proteins and systems in the organism. Preclinical studies reported that sigma-1 receptor expression correlates with the clinical manifestation of disease. […]
Cal‘MAM’ity at the Endoplasmic Reticulum-Mitochondrial Interface: A Potential Therapeutic Target for Neurodegeneration and Human Immunodeficiency Virus-Associated Neurocognitive Disorders
By Jessica Proulx, In-Woo Park, and Kathleen Borgmann Excerpt from the article published in Frontiers in neuroscience, 15, 715945. https://doi.org/10.3389/fnins.2021.715945 Editor’s Highlights Cooperation and communication between the ER and mitochondria are essential to ensure maintenance of neuronal and organelle homeostasis. Neurons are not directly infected by HIV-1; thus, indirect HIV-induced toxicity via infected glia is a key mechanism […]
Highly Specific Sigma Receptor Ligands Exhibit Anti-Viral Properties in SARS-CoV-2 Infected Cells
by Ostrov, D.A.; Bluhm, A.P.;Li, D.; Khan, J.Q.; Rohamare, M.;Rajamanickam, K.; K. Bhanumathy,K.; Lew, J.; Falzarano, D.;Vizeacoumar, F.J.; et al. Excerpt from the article published in Pathogens 2021,10, 1514. https://doi.org/10.3390/pathogens10111514 Editor’s Highlights Background There is a strong need for prevention and treatment strategies for COVID-19 that are not impacted by SARS-CoV-2 mutations emerging in variants […]
Sigma-1 Receptor: A Potential Therapeutic Target for Traumatic Brain Injury
By Shi Mingming, Chen Fanglian, Chen Zhijuan, Yang Weidong, Yue Shuyuan, Zhang Jianning, and Chen Xin Excerpt from the article published in Frontiers in Cellular Neuroscience, 2021. DOI:10.3389/fncel.2021.685201 Editor’s Highlights Abstract The sigma-1 receptor (Sig-1R) is a chaperone receptor that primarily resides at the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) and acts as a dynamic […]
Sigma-1 receptor regulates mitophagy in dopaminergic neurons and contributes to dopaminergic protection
by Mingmei Wang, Chunlei Wan, Tao He, Chaojun Han, Kailian Zhu, John L.Waddington, Xuechu Zhen Excerpt from the article published in Neuropharmacology, 15 September 2021 | https://doi.org/10.1016/j.neuropharm.2020.108360 Editor’s Highlights Abstract Mitochondria are essential for neuronal survival and function, and mitochondrial dysfunction plays a critical role in the pathological development of Parkinson’s disease (PD). Mitochondrial quality control […]
Sigma-1R Protects Retinal Ganglion Cells in Optic Nerve Crush Model for Glaucoma
By Linya Li, Shaoqing He, Yang Liu, Thomas Yorio, Dorette Z. Ellis Excerpt from the article published in Investigative Ophthalmology & Visual Science August 2021, Vol.62, 17. doi: https://doi.org/10.1167/iovs.62.10.17 Editor’s Highlights Degeneration of the retinal ganglion cells (RGCs), their axons, and optic nerves (ONs) are hallmarks in glaucoma. The Sigma-1R (σ-1r) is localized at the endoplasmic […]
Sigma 1 Receptor, Cholesterol and Endoplasmic Reticulum Contact Sites
By Vladimir Zhemkov, Jen Liou, and Ilya Bezprozvanny Excerpt from the article published in Contact. January 2021. doi:10.1177/25152564211026505 Editor’s Highlights The endoplasmic reticulum (ER) is the largest cellular organelle and its function is to produce proteins for the rest of the cell to function. The ER membrane is organized into sub-compartments where specific signaling and […]
Sigmar1’s Molecular, Cellular, and Biological Functions in Regulating Cellular Pathophysiology
By Aishwarya Richa, Abdullah Chowdhury S., Morshed Mahboob, Remex Naznin Sultana, and Bhuiyan Md. Shenuarin Excerpt from the article published in Frontiers in Physiology, volume 12, 2021. DOI: https://doi.org/10.3389/fphys.2021.705575 Editor’s Highlights Sigma-1 receptor is a multifunctional, ubiquitously expressed chaperone protein encoded by the SIGMAR1 gene. Alterations in Sigmar1’s subcellular localization, expression, and signaling have been […]
Visualization of Dynamic Expression of Myocardial Sigma-1 Receptor After Myocardial Ischemia and Reperfusion Using Radioiodine-Labeled 2-[4-(2-iodophenyl)piperidino]cyclopentanol (OI5V) Imaging
By Hiroshi Wakabayashi, Junichi Taki, Hiroshi Mori, Tomo Hiromasa, Norihito Akatani, Anri Inaki, Takashi Kozaka, Kazuhiro Shiba, Kazuma Ogawa, Seigo Kinuya Excerpt from the article published in Circulation Journal, Article ID CJ-21-0320, Online ISSN 1347-4820, Print ISSN 1346-9843, DOI: https://doi.org/10.1253/circj.CJ-21-0320 Editor’s Highlights The sigma-1 receptor chaperone (σ1R) is considered as a pluripotent modulator with resultant multiple functional manifestations in […]
Sigma-1 Receptor Promotes Mitochondrial Bioenergetics by Orchestrating ER Ca2+ Leak during Early ER Stress
By Koshenov, Z.; Oflaz, F.E.; Hirtl, M.; Pilic, J.; Bachkoenig, O.A.; Gottschalk, B.; Madreiter-Sokolowski, C.T.; Rost, R.; Malli, R.; Graier, W.F. Excerpt from the article published in Metabolites 2021, 11, 422. Published: 26 June 2021, DOI: https://doi.org/10.3390/metabo11070422 Editor’s Highlights The endoplasmic reticulum (ER) is a complex, multifunctional organelle of eukaryotic cells and responsible for the trafficking and […]
The Unfolded Protein Response in Immune Cells as an Emerging Regulator of Neuroinflammation
By Dominique Fernández, Antonia Geisse, Jose Ignacio Bernales, Alonso Lira, and Fabiola Osorio Excerpt from the article published in Frontiers of Aging Neuroscience, 11 June 2021, Sec. Cellular and Molecular Mechanisms of Brain-aging, DOI: https://doi.org/10.3389/fnagi.2021.682633 Editor’s Highlights Cells possess regulatory mechanisms that maintain proteostasis in conditions that overload the folding capacity of the organelle (a […]
The Role of Astrocytes in the Neurorepair Process
By Raphaela Almeida Chiareli, Gustavo Almeida Carvalho, Bruno Lemes Marques, Lennia Soares Mota, Onésia Cristina Oliveira-Lima, Rodrigo Mello Gomes, Alexander Birbrair, Renato Santiago Gomez, Fabrício Simão, Friederike Klempin, Marcel Leist, and Mauro Cunha Xavier Pinto Excerpt from the article published in Frontiers in Cell and Developmental Biology, 25 May 2021 | https://doi.org/10.3389/fcell.2021.665795 Editor’s Highlights Astrocytes […]
The role of sigma 1 receptor in organization of endoplasmic reticulum signaling microdomains
By Vladimir Zhemkov, Jonathon A Ditlev, Wan-Ru Lee, Mikaela Wilson, Jen Liou, Michael K Rosen, Ilya Bezprozvanny Excerpt from the article published in eLife 2021;10:e65192 DOI: 10.7554/eLife.65192 Editor’s Highlights Sigma-1 receptor (S1R) modulates many physiological processes, such as cell excitability, transcriptional activity, Ca2+ homeostasis, stress response, and autophagy. Many biological functions of the Sigma-1 receptor can be explained […]
Sigma-1 Receptor Interaction with Cholesterol: Mechanisms of S1R Activation and Its Role in Neurodegenerative Diseases
by Zhemkov V, Geva M, Hayden MR, Bezprozvanny I Excerpt from the article published in Int J Mol Sci. 2021;22(8):4082. Published 2021 Apr 15. https://doi.org/10.3390/ijms22084082 Editor’s Highlights The Sigma-1 receptor (S1R) is a well-established target for the treatment of neurodegenerative disorders, and it plays a key role in neurodegenerative diseases. Some variants of the S1R […]
Negative Impact of Sigma-1 Receptor Agonist Treatment on Tissue Integrity and Motor Function Following Spinal Cord Injury
By Alise Lattard, Gaëtan Poulen, Sylvain Bartolami, Yannick N. Gerber, and Florence E. Perrin Excerpt from the article published in Frontiers in Pharmacology, 10 February 2021Sec. Neuropharmacology, Volume 12 – 2021, DOI: https://doi.org/10.3389/fphar.2021.614949 Editors Highlights Abstract In traumatic spinal cord injury, the initial trauma is followed by a cascade of impairments, including excitotoxicity and calcium […]
Genomic Action of Sigma-1 Receptor Chaperone Relates to Neuropathic Pain
By Shao-Ming Wang, Nino Goguadze, Yuriko Kimura, Yuko Yasui, Bin Pan, Tzu-Yun Wang, Yoki Nakamura, Yu-Ting Lin, Quinn H. Hogan, Katherine L. Wilson, Tsung-Ping Su, and Hsiang-en Wu Excerpt from the article published in Molecular Neurobiology volume 58, pages 2523–2541 (2021) DOI: https://doi.org/10.1007/s12035-020-02276-8 Editor’s Highlights Neuropathic pain is one of the most debilitating forms of […]
Stimulation of Sigma-1 Receptor Protects against Cardiac Fibrosis by Alleviating IRE1 Pathway and Autophagy Impairment
By Jing Qu, Miaoling Li, Dongxu Li, Yanguo Xin, Junli Li, Song Lei, Wenchao Wu, and Xiaojing Liu Excerpt from the article published in Oxidative medicine and cellular longevity vol. 2021 8836818. 4 Jan. 2021, DOI:10.1155/2021/8836818 Editor’s Highlights Cardiac fibrosis is a common pathological process in the development of various cardiovascular diseases and the risk for […]
Regulation of membrane NMDA receptors by dynamics and protein interactions
By Mar Petit-Pedrol and Laurent Groc Excerpt from the article published in Journal of Cell Biology 4 January 2021; 220 (1): e202006101. doi: https://doi.org/10.1083/jcb.202006101 Editor’s Highlights The N-methyl-D-aspartate receptors (NMDARs) are ionotropic glutamate receptors whose activation and calcium permeability play central roles in glutamate synapse physiology. NMDARs form protein–protein interactions with several transmembrane neurotransmitter receptors and ion channels […]
The Sigma 2 receptor promotes and the Sigma 1 receptor inhibits mu-opioid receptor-mediated antinociception
By Sánchez-Blázquez, P., Cortés-Montero, E., Rodríguez-Muñoz, M. et al. Excerpt from the article published in Mol Brain 13, 150 (2020). https://doi.org/10.1186/s13041-020-00676-4 Editor’s Highlights σ2R is essential for the antinociceptive effects of exogenous and endogenous ligands of MOR but not for the antinociceptive effects of other families of G-receptors that also mediate analgesia, such as DOR, CB1R and α2AR. […]
Sigma-1 receptor chaperones rescue nucleocytoplasmic transport deficit seen in cellular and Drosophila ALS/FTD models
By Pin-Tse Lee, Jean-Charles Liévens, Shao-Ming Wang, Jian-Ying Chuang, Bilal Khalil, Hsiang-en Wu, Wen-Chang Chang, Tangui Maurice, and Tsung-Ping Su Excerpt from the article published in Nature Communications 11, 5580 (2020). https://doi.org/10.1038/s41467-020-19396-3 Editor’s Highlights Amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD), either sporadic or familial, share a (G4C2)-RNA hexanucleotide repeat expansion (HRE) upstream of […]
Chaperone Sigma1R and Antidepressant Effect
By Mikhail V. Voronin, Yulia V. Vakhitova, and Sergei B. Seredenin Excerpt from the article published in International Journal of Molecular Sciences 2020 Oct; 21(19): 7088. Published 2020 Sep 25. DOI: 10.3390/ijms21197088 Editor’s Highlights Antidepressant use is accompanied by various side effects, and about one-third of patients do not achieve remission. Sigma-1 receptor (Sigma1R) acts as a chaperone to stabilize […]
Sigma-1 receptor ablation impedes adipocyte-like differentiation of mouse embryonic fibroblasts
By Huan Yang, Hongtao Shen, Jing Li, Kristin I. Stanford, and Lian-Wang Guo Excerpt from the article published in Cell Signal. 2020 Nov;75:109732. DOI: 10.1016/j.cellsig.2020.109732. Epub 2020 Aug 2. PMID: 32750415; PMCID: PMC7530065. Editor’s Highlights Abstract The sigma-1 receptor (Sig1R) is a unique ligand-operated endoplasmic reticulum (ER) protein without any mammalian homolog. It has long […]
Distinct Regulation of σ1 Receptor Multimerization by Its Agonists and Antagonists in Transfected Cells and Rat Liver Membranes
By Weimin Conrad Hong Excerpt from the article published in Journal of Pharmacology and Experimental Therapeutics, May 2020, 373 (2) 290-301; DOI: https://doi.org/10.1124/jpet.119.262790 Editor’s Highlights The sigma-1 receptor (σ1R) interacts with and modulates the activity of a plethora of partner proteins, including channels, receptors, and transporters, and regulates their function. Changes in σ1R oligomerization by ligands can modulate the availability of σ1R […]
Sigma‐1 receptor protects against ferroptosis in hepatocellular carcinoma cells
By Tao Bai, Pengxu Lei, Hao Zhou, Ruopeng Liang, Rongtao Zhu, Weijie Wang, Lin Zhou, and Yuling Sun Excerpt from the article published in Journal of Cellular and Molecular Medicine 2019 Nov; 23(11): 7349–7359. DOI: 10.1111/jcmm.14594 Editor’s Highlights Hepatocellular carcinoma (HCC) is a common type of cancer that is ranked sixth in prevalence and third in mortality worldwide. […]
Neuronal Sigma-1 Receptors: Signaling Functions and Protective Roles in Neurodegenerative Diseases
by Daniel A. Ryskamp, Svetlana Korba, Vladimir Zhemkov, Nina Kraskovskaya, and Ilya Bezprozvanny Excerpt from the article published in Front. Neurosci., 28 August 2019 | https://doi.org/10.3389/fnins.2019.00862 Editor’s Highlights Abstract Sigma-1 receptor (S1R) is a multi-functional, ligand-operated protein situated in endoplasmic reticulum (ER) membranes and changes in its function and/or expression have been associated with various neurological disorders including amyotrophic lateral sclerosis/frontotemporal dementia, […]
Sigma-1 receptor modulates neuroinflammation associated with mechanical hypersensitivity and opioid tolerance in a mouse model of osteoarthritis pain
By Mireia Carcolé, Sami Kummer, Leonor Gonçalves, Daniel Zamanillo, Manuel Merlos, Anthony H. Dickenson, Begoña Fernández-Pastor, David Cabañero, and Rafael Maldonado Excerpt from the article published in British Journal of Pharmacology, 23 July 2019; 176: 3939– 3955. DOI: https://doi.org/10.1111/bph.14794 Abstract Background and Purpose: Osteoarthritic pain is a chronic disabling condition lacking effective treatment. Continuous use of opioid drugs during […]
The Sigma-1 Receptor in Cellular Stress Signaling
By Teruo Hayashi Excerpt from the article published in Frontiers in Neuroscience, 16 July 2019 | https://doi.org/10.3389/fnins.2019.00733 Editor’s Highlights The sigma-1 receptor (Sig-1R)’s structure, is an integral endoplasmic reticulum (ER) membrane protein which shares no homology with any other mammalian protein. Sig-1R is enriched in a specialized ER subdomain which physically contacts the mitochondria, called the […]
Blockade of the Sigma-1 Receptor Relieves Cognitive and Emotional Impairments Associated to Chronic Osteoarthritis Pain
By Mireia Carcolé, Daniel Zamanillo, Manuel Merlos, Begoña Fernández-Pastor, David Cabañero, and Rafael Maldonado Excerpt from the article published in Frontiers in Pharmacology, 03 May 2019Sec. Experimental Pharmacology and Drug Discovery DOI: https://doi.org/10.3389/fphar.2019.00468 Abstract Osteoarthritis is the most common musculoskeletal disease worldwide, often characterized by degradation of the articular cartilage, chronic joint pain and disability. Cognitive dysfunction, […]
Molecular Interplay Between the Sigma-1 Receptor, Steroids, and Ion Channels
By Sara L. Morales-Lázaro, Ricardo González-Ramírez, and Tamara Rosenbaum Excerpt from the article published in Frontiers in Pharmacology, 10.,24 April 2019Sec. Experimental Pharmacology and Drug Discovery, DOI: https://doi.org/10.3389/fphar.2019.00419 Editor’s Highlights Abstract Cell excitability is tightly regulated by the activity of ion channels that allow for the passage of ions across cell membranes. Ion channel activity is […]
Modulation of the Sigma-1 Receptor-IRE1 pathway is beneficial in preclinical models of inflammation and sepsis.
By Dorian A Rosen, Scott M. Seki, Anthony Fernández-Castañeda, Rebecca M. Beiter, Jacob D. Eccles, Judith A. Woodfolk, and Alban Gaultier Excerpt from the author manuscript published in Science translational medicine, 2019 Feb 6; 11(478): eaau5266. available here https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936250/#!po=28.9474 Editor’s Highlights The endoplasmic reticulum (ER) is increasingly recognized as a powerful controller of inflammatory signaling and […]
SIGMAR1/Sigma-1 receptor ablation impairs autophagosome clearance
By Huan Yang, Hongtao Shen, Jing Li, and Lian-Wang Guo Excerpt from the article published in Autophagy, 15:9, 1539-1557, Published online: 14 Mar 2019 DOI: 10.1080/15548627.2019.1586248 Editor’s Highlights Autophagy lysosome-mediated pathway (ALP) degrades and recycles cellular wastes including proteins, lipids, and dysfunctional organelles, and is a key element of the Proteostasis Network. SIGMAR1 is a putative chaperone protein primarily […]
Sigma-1 Receptor Activation Induces Autophagy and Increases Proteostasis Capacity In Vitro and In Vivo
By Maximilian G. Christ, Heike Huesmann, Heike Nagel, Andreas Kern and Christian Behl Excerpt from the article published in Cells. 2019; 8(3):211. DOI: https://doi.org/10.3390/cells8030211 Editor’s Highlights The control and maintenance of proteome integrity and proteostasis are of utmost importance. Cellular proteostasis includes protein folding, protein assembly, refolding of damaged proteins, as well as protein degradation, […]
Cardiac Dysfunction in the Sigma 1 Receptor Knockout Mouse Associated With Impaired Mitochondrial Dynamics and Bioenergetics
By Chowdhury S. Abdullah, Shafiul Alam, Richa Aishwarya, Sumitra Miriyala, Manikandan Panchatcharam, Mohammad Alfrad Nobel Bhuiyan, Jonette M. Peretik, A. Wayne Orr, Jeanne James, Hanna Osinska, Jeffrey Robbins, John N. Lorenz, and Md. Shenuarin Bhuiyan Excerpt from the article published in Journal of the American Heart Association. 2018;7:e009775, 11 Oct 2018, DOI: https://doi.org/10.1161/JAHA.118.009775 Editor’s Highlights […]
Small-Molecule Sigma1 Modulator Induces Autophagic Degradation of PD-L1
By Christina M. Maher; Jeffrey D. Thomas; Derick A. Haas; Charles G. Longen; Halley M. Oyer; Jane Y. Tong; and Felix J. Kim Excerpt from the article published in Molecular Cancer Research, Volume 16, Issue 2; 1 February 2018; 243–255; DOI: https://doi.org/10.1158/1541-7786.MCR-17-0166 Editor’s Highlights Abstract Emerging evidence suggests that Sigma1 (SIGMAR1, also known as sigma-1 […]
TRPV1 channels and the progesterone receptor Sig-1R interact to regulate pain
By Miguel Ortíz-Rentería, Rebeca Juárez-Contreras, Ricardo González-Ramírez, and Sara L. Morales-Lázaro Excerpt from the article published in PNAS, January 29, 2018, 115 (7) E1657-E1666, DOI: https://doi.org/10.1073/pnas.1715972115 Significance The TRPV1 ion channel has been widely associated with the generation of painful responses. The responses of cells expressing this ion channel and, presumably, the overall pain response of an […]
Roles of sigma-1 receptors on mitochondrial functions relevant to neurodegenerative diseases
By Tzu-Yu Weng, Shang-Yi Anne Tsai, and Tsung-Ping Su Excerpt from the article published in Journal of Biomedical Science 24, 74 (2017). https://doi.org/10.1186/s12929-017-0380-6 Editor’s highlights The sigma-1 receptor (Sig-1R) is a chaperone that resides mainly at the mitochondrion-associated endoplasmic reticulum (ER) membrane (called the MAMs) and acts as a dynamic pluripotent modulator in living systems. The Sig-1R […]
Sigma 1 receptor regulates ERK activation and promotes survival of optic nerve head astrocytes
By Jing Zhao, Barbara A. Mysona, Jing Wang, Graydon B. Gonsalvez, Sylvia B. Smith, and Kathryn E. Bollinger Excerpt from the article published in PLOS ONE, September 12, 2017, DOI: https://doi.org/10.1371/journal.pone.0184421 Editor’s Highlights Neuronal and glial cell types throughout the retina and optic nerve contain sigma 1 receptor (S1R), and its agonists display robust neuroprotective […]
Sigma-1 receptor regulates Tau phosphorylation and axon extension by shaping p35 turnover via myristic acid
By Shang-Yi A. Tsai, Michael J. Pokrass, Neal R. Klauer, Hiroshi Nohara, and Tsung-Ping Su Excerpt from the article published in PNAS May 11, 2015, 112(21) 6742-6747 DOI: https://doi.org/10.1073/pnas.1422001112 Editor’s Highlights Malfunction of axonal maintenance, regeneration, and target recognition contribute to CNS disorders such as Parkinson’s disease (PD). Cyclin-dependent kinase (Cdk5) is a ubiquitously expressed enzyme; […]
Sigma-1 receptor agonist PRE084 is protective against mutant huntingtin-induced cell degeneration: involvement of calpastatin and the NF-κB pathway
By A. Hyrskyluoto, I. Pulli, K. Törnqvist, T. Huu Ho, L. Korhonen, and D. Lindholm Excerpt from the article published in Cell Death Dis 4, e646 (2013). https://doi.org/10.1038/cddis.2013.170 Editor’s Highlights Huntington’s disease (HD) is an autosomal, dominantly inherited neurodegenerative disorder that is caused by an expansion of cytosine–adenine–guanine (CAG) repeats in the first exon of the huntingtin […]