ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2019
Pridopidine Induces Functional Neurorestoration Via the Sigma-1 Receptor in a Mouse Model of Parkinson's Disease.
Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 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
- Effects of Pridopidine on Functional Capacity in Early-Stage Participants from the PRIDE-HD Study.Journal of Huntington's disease · 2020Trial
- Modulation of the TGF-β/Smad Signaling Pathway by a Bioactive Oxidized Polygonati Rhizoma Polysaccharide Crosslinked Chitosan Hydrogel as Therapeutic Carrier for Parkinson's Disease Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Pridopidine Mediated Sigma-1 Receptor Activation and Therapeutic Implications in Neurodegenerative Diseases.Neurology international · 2026Review
- Alcohol withdrawal and the sigma receptor: exploring the link between withdrawal and cognitive impairment.Journal of neural transmission (Vienna, Austria : 1996) · 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
- 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 Search for Disease Modification in Parkinson's Disease-A Review of the Literature.Life (Basel, Switzerland) · 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
- Development of Carbon-11 Labeled Pyrimidine Derivatives as Novel Positron Emission Tomography (PET) Agents Enabling Brain Sigma-1 Receptor Imaging.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Nuclear pore dysfunction and disease: a complex opportunity.Nucleus (Austin, Tex.) · 2024Review
- Pridopidine subtly ameliorates motor skills in a mouse model for vanishing white matter.Life science alliance · 2024Article
- Targeting Sigma-1 Receptor: A Promising Strategy in the Treatment of Parkinson's Disease.Neurochemical research · 2023Review
- The Sigma Receptors in Alzheimer's Disease: New Potential Targets for Diagnosis and Therapy.International journal of molecular sciences · 2023Review
- Overview of Sigma-1R Subcellular Specific Biological Functions and Role in Neuroprotection.International journal of molecular sciences · 2023Review
- Chaperone-Dependent Mechanisms as a Pharmacological Target for Neuroprotection.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Pridopidine is a small molecule in clinical development for the treatment of Huntington's disease. It was recently found to have high binding affinity to the sigma-1 receptor, a chaperone protein involved in cellular defense mechanisms and neuroplasticity. Here, we have evaluated the neuroprotective and neurorestorative effects of pridopidine in a unilateral 6-hydroxydopamine (6-OHDA) lesion model of parkinsonism in mice. By 5 weeks of daily administration, a low dose of pridopidine (0.3 mg/kg) had significantly improved deficits in forelimb use (cylinder test, stepping test) and abolished the ipsilateral rotational bias typical of hemiparkinsonian animals. A higher dose of pridopidine (1 mg/kg) significantly improved only the rotational bias, with a trend towards improvement in forelimb use. The behavioral recovery induced by pridopidine 0.3 mg/kg was accompanied by a significant protection of nigral dopamine cell bodies, an increased dopaminergic fiber density in the striatum, and striatal upregulation of GDNF, BDNF, and phosphorylated ERK1/2. The beneficial effects of pridopidine 0.3 mg/kg were absent in 6-OHDA-lesioned mice lacking the sigma-1 receptor. Pharmacokinetic data confirmed that the effective dose of pridopidine reached brain concentrations sufficient to bind S1R. Our results are the first to show that pridopidine promotes functional neurorestoration in the damaged nigrostriatal system acting via the sigma-1 receptor.
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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.