Published research to date related to Sigma proteins and Amyotrophic Lateral Sclerosis (ALS) has been conducted with compounds not developed by Advantx Pharmaceuticals Inc. Our therapeutic candidate ADV368 is the first truly bispecific, pharmaceutical-grade compound in development targeting Sigma-1 and Sigma-2 receptors with a novel and clean molecule, far superior in potency, selectivity, safety, and efficacy to all others tested to date.
RECENT SCIENTIFIC PUBLICATIONS RELATED TO SIGMA RECEPTORS AND ALS
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 […]
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 […]
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 […]
Potential roles of the endoplasmic reticulum stress pathway in amyotrophic lateral sclerosis
By Yu-Mi Jeon, Younghwi Kwon, Shinrye Lee, and Hyung-Jun Kim Excerpt from the article published in Frontiers in Aging Neuroscience, 15 February 2023. DOI: https://doi.org/10.3389/fnagi.2023.1047897 Editor’s Highlights Abstract The endoplasmic reticulum (ER) is a major organelle involved in protein quality control and cellular homeostasis. ER stress results from structural and functional dysfunction of the organelle, along […]
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 […]
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 […]
Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation
By Richard J. Mead, Ning Shan, H. Joseph Reiser, Fiona Marshall, and Pamela J. Shaw Excerpt from the article published in Nature Reviews Drug Discovery, 21 December 2022. DOI: https://doi.org/10.1038/s41573-022-00612-2 Abstract Amyotrophic lateral sclerosis (ALS) is a devastating disease caused by degeneration of motor neurons. As with all major neurodegenerative disorders, development of disease-modifying therapies […]
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 Impact of Mitochondrial Dysfunction in Amyotrophic Lateral Sclerosis
By Jiantao Zhao, Xuemei Wang, Zijun Huo, Yanchun Chen, Jinmeng Liu, Zhenhan Zhao, Fandi Meng, Qi Su, Weiwei Bao, Lingyun Zhang, Shuang Wen, Xin Wang, Huancai Liu, and Shuanhu Zhou Excerpt from the article published in Cells 11, no. 13: 2049. Published: 28 June 2022. DOI: https://doi.org/10.3390/cells11132049 Editor’s Highlights Amyotrophic lateral sclerosis (ALS) is a rapidly […]
Endoplasmic Reticulum and/or Mitochondrial-Dependent Neuronal Degeneration in ALS
By Jennifer S. Sun Article published in NeurologyLive, June 2022, Volume 5, Issue 3 https://www.neurologylive.com/view/endoplasmic-reticulum-mitochondrial-dependent-neuronal-degeneration-als Editor’s Highlights The MAM-associated chaperone protein sigma 1 receptor (Sigma1R) is also involved in lipid export and calcium signaling through IP3R regulation. Agonists of Sigma1R have also been successful in protecting motor neurons and muscle activity in presymptomatic ALS mutSOD1 mice and in […]
Towards Understanding the Relationship Between ER Stress and Unfolded Protein Response in Amyotrophic Lateral Sclerosis
By Chenxuan Zhao, Yong Liao, Abdul Rahaman, and Vijay Kumar Excerpt from the article published in Frontiers in Aging Neuroscience, 15 June 2022, DOI: https://doi.org/10.3389/fnagi.2022.892518 Editor Highlights Protein misfolding and aggregation in cells trigger the ER stress which is overpowered by an adaptive response of cells collectively known as unfolded protein response (UPR). Endoplasmic reticulum […]
Targeting ER-Mitochondria Signaling as a Therapeutic Target for Frontotemporal Dementia and Related Amyotrophic Lateral Sclerosis
By Sandra M. Martín-Guerrero, Andrea Markovinovic, Gábor M. Mórotz, Shaakir Salam, Wendy Noble and Christopher C. J. Miller Excerpt from the article published in Frontiers in Cell and Developmental Biology, volume 10, 27 May 2022 DOI: https://doi.org/10.3389/fcell.2022.915931 Editor’s Highlights Endoplasmic reticulum (ER) and mitochondria signaling is damaged in Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) […]
Novel reporters of mitochondria-associated membranes (MAM), MAMtrackers, demonstrate MAM disruption as a common pathological feature in amyotrophic lateral sclerosis
By Shohei Sakai, Seiji Watanabe, Okiru Komine, Akira Sobue, and Koji Yamanaka Excerpt from the article published in The FASEB Journal. 2021; 35:e21688. pPublished: 18 June 2021, DOI: https://doi.org/10.1096/fj.202100137R Editor’s Highlights Aberrant regulation of MAM is associated with various neurological diseases, including amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease that selectively affects motor neurons. MAM disruption is […]
Wildtype σ1 receptor and the receptor agonist improve ALS-associated mutation-induced insolubility and toxicity
By Yasuharu Shinoda, Yudai Haga, Koichiro Akagawa, and Kohji Fukunaga Excerpt from the article published in Journal of Biological Chemistry . 2020 Dec 18;295(51):17573-17587. PMID: 33453999; PMCID: PMC7762949. DOI: 10.1074/jbc.RA120.015012 Editor’s Highlights Genetic mutations related to ALS, a progressive neurological disease, have been discovered in the gene encoding σ-1 receptor (σ1R). σ1R localizes preferentially to the […]
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 […]
Amyotrophic Lateral Sclerosis: Proteins, Proteostasis, Prions, and Promises
By Luke McAlary, Yee Lian Chew, Jeremy Stephen Lum, Nicholas John Geraghty, Justin John Yerbury, and Neil R. Cashman Excerpt from the article published in Frontiers in Cellular Neuroscience, volume 14, 2020, DOI: https://doi.org/10.3389/fncel.2020.581907 Editor’s Highlights The disease mechanisms of Amyotrophic lateral sclerosis (ALS) strongly implicates a pathological role for both declining proteostasis and prion-like […]
The ALS-Related σ1R E102Q Mutant Eludes Ligand Control and Exhibits Anomalous Response to Calcium
By María Rodríguez-Muñoz, Elsa Cortés-Montero, Javier Garzón-Niño, and Pilar Sánchez-Blázquez Excerpt from the article published in International Journal of Molecular Sciences, 2020, 21, no. 19: 7339. https://doi.org/10.3390/ijms21197339 Editor’s Highlights Mutations in human SIGMAR1 are associated with motor neuron diseases such as autosomal recessive distal hereditary motor neuropathy and juvenile amyotrophic lateral sclerosis (ALS). A single missense […]
Proteostasis Failure in Neurodegenerative Diseases: Focus on Oxidative Stress
By Annika Höhn, Antonella Tramutola, and Roberta Cascella Excerpt from the article published in OMCL Oxidative Medicine and Cellular Longevity 1942-0994 1942-0900 Hindawi Volume 2020 Article ID 5497046 DOI: https://doi.org/10.1155/2020/5497046 Editor’s Highlights The cellular protein quality control ensures the proper folding of newly synthesized proteins, handling unfolding, refolding, and/or degradation of misfolded proteins. This process is critical as 30% of newly synthesized proteins are prone […]
Sigma-1 receptor is a key genetic modulator in amyotrophic lateral sclerosis
By Simon Couly, Bilal Khalil, Véronique Viguier, Julien Roussel, Tangui Maurice, and Jean-Charles Liévens Excerpt from the article published in Human Molecular Genetics, Volume 29, Issue 4, 15 February 2020, Pages 529–540, https://doi.org/10.1093/hmg/ddz267 Editor’s Highlights The Sigma-1 receptor (S1R) is a transmembrane protein mostly located in the endoplasmic reticulum (ER), that presents a main bulk in […]
The Glu102 mutation disrupts higher-order oligomerization of the sigma 1 receptor
By Ara M. Abramyan, Hideaki Yano, Min Xu, Leanne Liu, Sett Naing, Andrew D. Fant, and Lei Shi Excerpt from the article published in Computational and Structural Biotechnology Journal, Volume 18, 2020, Pages 199-206, ISSN 2001-0370, DOI: https://doi.org/10.1016/j.csbj.2019.12.012. Editor’s Highlights The E102Q mutation of σ1R has been found to elicit familial cases of amyotrophic lateral […]