ArticleNeurobiology of disease2019
Pridopidine protects neurons from mutant-huntingtin toxicity via the sigma-1 receptor.
Article in Neurobiology of disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- A neuroprotective target in the shadows: a scoping review of pharmacological gaps in σ1R agonists for glutamate-induced neurotoxicity.Frontiers in pharmacology · 2026Pooled it
- Pridopidine in early-stage manifest Huntington's disease: a phase 3 trial.Nature medicine · 2025Trial
- Effects of Pridopidine on Functional Capacity in Early-Stage Participants from the PRIDE-HD Study.Journal of Huntington's disease · 2020Trial
- Review
- Pridopidine Mediated Sigma-1 Receptor Activation and Therapeutic Implications in Neurodegenerative Diseases.Neurology international · 2026Review
- Targeting endoplasmic reticulum stress and protein misfolding in schizophrenia: the emerging promise of sigma-1 receptor agonists.Psychopharmacology · 2026Review
- Pridopidine Protects ALS Patient-Derived Neural Progenitor Cells via Sigma-1 Receptor Activation.International journal of molecular sciences · 2026Article
- An integrative neuropharmacological review of Huntington's disease challenges and the role of novel formulations in addressing pharmacological‒pharmaceutical limitations.Frontiers in pharmacology · 2026Review
- Pridopidine, a Potent and Selective Therapeutic Sigma-1 Receptor (S1R) Agonist for Treating Neurodegenerative Diseases.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Sigma-2 Receptor Antagonism Enhances the Neuroprotective Effects of Pridopidine, a Sigma-1 Receptor Agonist, in Huntington's Disease.Molecular neurobiology · 2025Article
- The complex web of membrane contact sites in brain aging and neurodegeneration.Cellular and molecular life sciences : CMLS · 2025Review
- Targeting the sigma-1 receptor with pridopidine induces functional neurorestoration in spinal cord ischemia-reperfusion injury.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Pharmacological and Pathological Implications of Sigma-1 Receptor in Neurodegenerative Diseases.Biomedicines · 2025Review
- Sigma 1 Receptor and Its Pivotal Role in Neurological Disorders.ACS pharmacology & translational science · 2025Review
- Brain-Derived Neurotrophic Factor (BDNF) in Huntington's Disease: Neurobiology and Therapeutic Potential.Current neuropharmacology · 2025Review
- Nuclear pore dysfunction and disease: a complex opportunity.Nucleus (Austin, Tex.) · 2024Review
- Fluvoxamine Exerts Sigma-1R to Rescue Autophagy via Pom121-Mediated Nucleocytoplasmic Transport of TFEB.Molecular neurobiology · 2024Article
- Huntington's Disease Drug Development: A Phase 3 Pipeline Analysis.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Highly specific σbioRxiv : the preprint server for biology · 2023Article
- Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Huntington's disease (HD) is a neurodegenerative disease caused by a CAG repeat expansion in the Huntingtin gene (HTT), translated into a Huntingtin protein with a polyglutamine expansion. There is preferential loss of medium spiny neurons within the striatum and cortical pyramidal neurons. Pridopidine is a small molecule showing therapeutic potential in HD preclinical and clinical studies. Pridopidine has nanomolar affinity to the sigma-1 receptor (sigma-1R), which is located predominantly at the endoplasmic reticulum (ER) and mitochondrial associated ER membrane, and activates neuroprotective pathways. Here we evaluate the neuroprotective effects of pridopidine against mutant Huntingtin toxicity in mouse and human derived in vitro cell models. We also investigate the involvement of the sigma-1 receptor in the mechanism of pridopidine. Pridopidine protects mutant Huntingtin transfected mouse primary striatal and cortical neurons, with an EC50 in the mid nanomolar range, as well as HD patient-derived induced pluripotent stem cells (iPSCs). This protection by pridopidine is blocked by NE-100, a purported sigma-1 receptor antagonist, and not blocked by ANA-12, a reported TrkB receptor antagonist. 3PPP, a documented sigma-1 receptor agonist, shows similar neuroprotective effects. Genetic knock out of the sigma-1 receptor dramatically decreases protection from pridopidine and 3PPP, but not protection via brain derived neurotrophic factor (BDNF). The neuroprotection afforded by pridopidine in our HD cell models is robust and sigma-1 receptor dependent. These studies support the further development of pridopidine, and other sigma-1 receptor agonists as neuroprotective agents for HD and perhaps for other disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.