Sigma and Parkinson's disease

Published research to date related to Sigma proteins and Parkinson’s disease have been conducted with compounds not developed by Advantx Pharmaceuticals Inc. Our therapeutic candidate ADV127 PD for Parkinson’s disease is the first truly selective, pharmaceutical-grade compound in development targeting the Sigma-1 receptor with a clean molecule and unambiguous agonist activity, far superior in potency, selectivity, safety, and efficacy to all others tested to date.


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: 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 […]

Ubiquilin-2 regulates pathological alpha-synuclein

By Stephanie S. Sandoval-Pistorius, Julia E. Gerson, Nyjerus Liggans, Jaimie H. Ryou, Kulin Oak, Xingli Li, Keyshla Y. Negron-Rios, Svetlana Fischer, Henry Barsh, Emily V. Crowley, Mary E. Skinner, Lisa M. Sharkey, Sami J. Barmada, and Henry L. Paulson Excerpt from the article published in Scientific Reports 13, 293 (2023). 06 January 2023, DOI: Editor’s […]

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: Editor’s Highlights Abstract Modern pharmacotherapy of neurodegenerative diseases is predominantly symptomatic and does not allow vicious circles causing disease […]

Impaired migratory phenotype of CD4+ T cells in Parkinson’s disease

By Dejan Mamula, Shervin Khosousi, Yachao He, Vesna Lazarevic, and Per Svenningsson Excerpt from the article published in NPJ Parkinsons Dis. 8, 171, 10 December 2022. DOI: Editor’s Highlights Abstract Dysfunctions in the immune system appear implicated in both disease onset and progression of Parkinson’s disease (PD). Neurodegeneration observed in the brain of PD patients has […]

A postmortem study suggests a revision of the dual-hit hypothesis of Parkinson’s disease

By Per Borghammer, Mie Kristine Just, Jacob Horsager, Casper Skjærbæk, Anna Raunio, Eloise H. Kok, Sara Savola, Shigeo Murayama, Yuko Saito, Liisa Myllykangas, and Nathalie Van Den Berge Excerpt from the article published in npj-Parkinson’s Disease. 8, 166, 30 November 2022, DOI: Editor’s Highlights Abstract The dual-hit hypothesis of Parkinson’s disease (PD) originally postulated that […]

Mitochondrial biogenesis, telomere length and cellular senescence in Parkinson’s disease and Lewy body dementia

By Muhammad Asghar, Amani Odeh, Ahmad Jouni Fattahi, Alexandra Edwards Henriksson, Aurelie Miglar, Shervin Khosousi, and Per Svenningsson Excerpt from the article published in Scientific Reports 12, 17578, 20 October 2022, DOI: Editor’s Highlights Although Parkinson’s disease (PD) is a complex disease with several causes, including genetic and environmental factors, progressive age remains the single […]

Small soluble α-synuclein aggregates are the toxic species in Parkinson’s disease

By Derya Emin, Yu P. Zhang, Evgeniia Lobanova, Alyssa Miller, Xuecong Li, Zengjie Xia, Helen Dakin, Dimitrios I. Sideris, Jeff Y. L. Lam, Rohan T. Ranasinghe, Antonina Kouli, Yanyan Zhao, Suman De, Tuomas P. J. Knowles, Michele Vendruscolo, Francesco S. Ruggeri, Franklin I. Aigbirhio, Caroline H. Williams-Gray, and David Klenerman Excerpt from the article published […]

Age-dependent neurodegeneration and neuroinflammation in a genetic A30P/A53T double-mutated α-synuclein mouse model of Parkinson’s disease

By Lisa Rauschenberger, Jennifer Behnke, Alexander Grotemeyer, Susanne Knorr, Jens Volkmann, and Chi Wang Excerpt from the article published in Neurobiology of Disease, Volume 171, September 2022, 105798, ISSN 0969-9961, DOI: Editor’s Highlights Authors’ Highlights Abstract The pathogenesis of Parkinson’s disease (PD) is closely interwoven with the process of aging. Moreover, increasing evidence from human postmortem […]

Lysosomal exocytosis releases pathogenic α-synuclein species from neurons in synucleinopathy models

By Ying Xue Xie, Nima N. Naseri, Jasmine Fels, Parinati Kharel, Yoonmi Na, Diane Lane, Jacqueline Burré, and Manu Sharma Excerpt from the article published in Nature Communications 13, 4918, 22 August 2022, DOI: Editor’s Highlights The release of pathogenic aggregates of the neuronal protein α-Synuclein (αSyn) into the extracellular space instigate the neuron-to-neuron transmission […]

Targeting Molecular Mediators of Ferroptosis and Oxidative Stress for Neurological Disorders

By Jing Li, Bowen Jia, Ying Cheng, Yiting Song, Qianqian Li, and Chengliang Luo Excerpt from the article published in Oxidative Medicine and Cellular Longevity, Volume 2022, Article ID 3999083, Published 22 Jul 2022, DOI: Editor’s Highlights Abstract As a novel mode of regulated cell death (RCD), ferroptosis was firstly proposed by Dixon in 2012 [1]. With […]

Amyloid β, Tau, and α-Synuclein aggregates in the pathogenesis, prognosis, and therapeutics for neurodegenerative diseases

By Urmi Senguptaab, and Rakez Kayedab Excerpt from the article published in Progress in Neurobiology, Volume 214, July 2022, 102270, ISSN 0301-0082, DOI: Autors’ Highlights Co-occurring proteinopathies confound disease diagnosis and treatment development. Overlapping Aβ, tau, and α-Syn pathologies are observed in AD and related diseases. Aβ, tau, and α-Syn converge directly or indirectly […]

TNF-α promotes α-synuclein propagation through stimulation of senescence-associated lysosomal exocytosis

By Eun-Jin Bae, Minsun Choi, Jeong Tae Kim, Dong-Kyu Kim, Min Kyo Jung, Changyoun Kim, Tae-Kyung Kim, Jun Sung Lee, Byung Chul Jung, Soo Jean Shin, Ka Hyun Rhee, and Seung-Jae Lee Excerpt from the article published in Experimental & Molecular Medicine (2022)(2022), Published: 05 July 2022, DOI: Editor’s Highligths Parkinson’s disease (PD), is […]

NMDA and AMPA Receptors at Synapses: Novel Targets for Tau and α-Synuclein Proteinopathies

By Maria Italia, Elena Ferrari, Monica Diluca, and Fabrizio Gardoni Excerpt from the article published in  Biomedicines 10, no. 7: 1550. Published: 29 June 2022 DOI: Editor’s Highlights Aberrant levels, post-translational modifications (PTMs), mislocalization, and aggregation of tau and α-synuclein have been widely described in Alzheimer’s disease (AD) and related tauopathies and Parkinson’s disease (PD) […]

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: 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 […]

Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson’s disease

By Tushar Kamath, Abdulraouf Abdulraouf, S. J. Burris, Jonah Langlieb, Vahid Gazestani, Naeem M. Nadaf, Karol Balderrama, Charles Vanderburg, and Evan Z. Macosko  Excerpt from the article published in Nature Neuroscience (2022). Editor’s Highlights A single subtype of dopamine (DA) neurons, marked by the expression of the gene AGTR1 and spatially confined to the ventral tier of the […]

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: 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 […]

Metabolomics and biochemical alterations caused by pleiotrophin in the 6-hydroxydopamine mouse model of Parkinson’s disease

By Esther Gramage, Jorge Sáiz, Rosalía Fernández-Calle, Yasmina B. Martín, María Uribarri, Marcel Ferrer-Alcón, Coral Barbas, and Gonzalo Herradón Excerpt from the article published in Scientific Reports volume 12, Article number: 3577 (2022) DOI Editor’s Highlights Parkinson’s disease (PD) is a neurodegenerative disorder that is characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN) and […]

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: 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 […]

Monitoring the interactions between alpha-synuclein and Tau in vitro and in vivo using bimolecular fluorescence complementation

By Laura Torres-Garcia, Joana M. P. Domingues, Edoardo Brandi, Caroline Haikal, Janitha M. Mudannayake, Inês C. Brás, Ellen Gerhardt, Wen Li, Alexander Svanbergsson, Tiago F. Outeiro, Gunnar K. Gouras, and Jia-Yi Li Excerpt from the article published in Scientific Reports volume 12, Article number: 2987 Published: 22 February 2022 DOI: Editor’s Highlights α-synuclein (aSyn) is […]

Lewy body disease or diseases with Lewy bodies?

By Kateřina Menšíková, Radoslav Matěj, Carlo Colosimo, Raymond Rosales, Lucie Tučková, Jiří Ehrmann, Dominik Hraboš, Kristýna Kolaříková, Radek Vodička, Radek Vrtěl, Martin Procházka, Martin Nevrlý, Michaela Kaiserová, Sandra Kurčová, Pavel Otruba, and Petr Kaňovský Excerpt from the article published in npj Parkinson’s Disease volume 8, Article number: 3 (2022). Published: 10 January 2022 DOI: […]

Therapeutics in the Pipeline Targeting α-Synuclein for Parkinson’s Disease

By Hilary Grosso Jasutkar, Stephanie E. Oh, and M. Maral Mouradian Excerpt from the article published in Pharmacological Reviews January 1, 2022,  74 (1) 207-237; DOI: Abstract Parkinson’s disease (PD) is the second most common neurodegenerative disorder and the fastest growing neurologic disease in the world, yet no disease-modifying therapy is available for this disabling condition. Multiple lines of […]

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  | 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 […]

GRP78 Overexpression Triggers PINK1-IP3R-Mediated Neuroprotective Mitophagy

By Tatiana Leiva-Rodríguez, David Romeo-Guitart, Mireia Herrando-Grabulosa, Pau Muñoz-Guardiola, Miriam Polo, Celia Bañuls Valerie Petegnief, Assumpció Bosch, Jose Miguel Lizcano, Nadezda Apostolova, Joaquim Forés, and Caty Casas Excerpt from the article published in Biomedicines 2021, 9, 1039. Published: 18 August 2021, DOI: Editor’s Highlights GRP78, also known as BiP or heat shock protein 5a (HSP5a), is […]

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. 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 […]

Genetic inactivation of the sigma-1 chaperone protein results in decreased expression of the R2 subunit of the GABA-B receptor and increased susceptibility to seizures

By Edijs Vavers, Baiba Zvejniece, Gundega Stelfa, Baiba Svalbe, Karlis Vilks, Einars Kupats, Rudolfs Mezapuke, Lasma Lauberte, Maija Dambrova, and Liga Zvejniece Excerpt from the article published in Neurobiology of Disease, Volume 150, 2021, 105244, ISSN 0969-9961, Editor’s Highlights The sigma-1 chaperone protein, also known as the sigma-1 receptor (Sig1R), in the cell plays […]

Sigma-2 receptor antagonists rescue neuronal dysfunction induced by Parkinson’s patient brain-derived α-synuclein

By Colleen S. Limegrover, Raymond Yurko, Nicholas J. Izzo, Kelsie M. LaBarbera, Courtney Rehak, Gary Look, Gilbert Rishton, Hank Safferstein, and Susan M. Catalano Excerpt from the article published in  Journals of Neuroscience Research; 99: 1161– 1176, 22 January 2021, DOI: Editor’s Highlights Oligomeric α-synuclein proteins found in Parkinson’s disease patient brain tissue cause neuron dysfunction. α-synuclein […]

Tau in the Pathophysiology of Parkinson’s Disease

By Lina Pan, Lanxia Meng, Mingyang He, and Zhentao Zhang Excerpt from the article published in Journal of Molecular Neuroscience 71, 2179–2191 (2021). DOI: Editor’s Highlights Parkinson’s disease (PD), one of the most common neurodegenerative diseases, is currently incurable. The progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the formation […]

α-Synuclein modulates tau spreading in mouse brains

By Fares Bassil, Emily S. Meymand, Hannah J. Brown, Hong Xu, Timothy O. Cox, Shankar Pattabhiraman, Chantal M. Maghames, Qihui Wu, Bin Zhang, John Q. Trojanowski, and Virginia M.-Y. Lee Excerpt from the article published in Journal of Experimental Medicine, 4 January 2021; 218 (1): e20192193. DOI: Editor’s Highlights Neuropathological data obtained from Parkinson’s disease (PD) […]

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: 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 […]

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 | 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 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: 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; […]