ArticleHuman molecular genetics2016
Pridopidine activates neuroprotective pathways impaired in Huntington Disease.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 79 citations in OpenAlex.
- Efficacy and Safety of VMAT-2 Inhibitors and Dopamine Stabilizers for Huntington's Chorea: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis.Medical sciences (Basel, Switzerland) · 2025Pooled it
- Pridopidine for the Improvement of Motor Function in Patients With Huntington's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.Frontiers in neurology · 2021Pooled 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
- Pridopidine, a Potent and Selective Therapeutic Sigma-1 Receptor (S1R) Agonist for Treating Neurodegenerative Diseases.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Sigma-1 Receptor Ligands for CNS Cancer Treatment.CNS drugs · 2025Review
- Sigma-2 Receptor Antagonism Enhances the Neuroprotective Effects of Pridopidine, a Sigma-1 Receptor Agonist, in Huntington's Disease.Molecular neurobiology · 2025Article
- Blueprint of Collapse: Precision Biomarkers, Molecular Cascades, and the Engineered Decline of Fast-Progressing ALS.International journal of molecular sciences · 2025Review
- Targeting the sigma-1 receptor with pridopidine induces functional neurorestoration in spinal cord ischemia-reperfusion injury.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Update on the Symptomatic Treatment of Huntington's Disease: From Pathophysiology to Clinical Practice.International journal of molecular sciences · 2025Review
- Pharmacological and Pathological Implications of Sigma-1 Receptor in Neurodegenerative Diseases.Biomedicines · 2025Review
- The Safety Profile of Pridopidine, a Novel Sigma-1 Receptor Agonist for the Treatment of Huntington's Disease.CNS drugs · 2025Article
- Third-Generation Antipsychotics: The Quest for the Key to Neurotrophism.Life (Basel, Switzerland) · 2025Review
- Brain-Derived Neurotrophic Factor (BDNF) in Huntington's Disease: Neurobiology and Therapeutic Potential.Current neuropharmacology · 2025Review
- Targeting Sigma-1 Receptor: A Promising Strategy in the Treatment of Parkinson's Disease.Neurochemical research · 2023Review
- Targeting Sigma Receptors for the Treatment of Neurodegenerative and Neurodevelopmental Disorders.CNS drugs · 2023Review
- Pridopidine Does Not Significantly Prolong the QTc Interval at the Clinically Relevant Therapeutic Dose.Neurology and therapy · 2023Article
- Nucleoporin POM121 signals TFEB-mediated autophagy via activation of SIGMAR1/sigma-1 receptor chaperone by pridopidine.Autophagy · 2023Article
Corrections and comments
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pridopidine has demonstrated improvement in Huntington Disease (HD) motor symptoms as measured by secondary endpoints in clinical trials. Originally described as a dopamine stabilizer, this mechanism is insufficient to explain the clinical and preclinical effects of pridopidine. This study therefore explored pridopidine's potential mechanisms of action. The effect of pridopidine versus sham treatment on genome-wide expression profiling in the rat striatum was analysed and compared to the pathological expression profile in Q175 knock-in (Q175 KI) vs Q25 WT mouse models. A broad, unbiased pathway analysis was conducted, followed by testing the enrichment of relevant pathways. Pridopidine upregulated the BDNF pathway (P = 1.73E-10), and its effect on BDNF secretion was sigma 1 receptor (S1R) dependent. Many of the same genes were independently found to be downregulated in Q175 KI mice compared to WT (5.2e-7 < P < 0.04). In addition, pridopidine treatment upregulated the glucocorticoid receptor (GR) response, D1R-associated genes and the AKT/PI3K pathway (P = 1E-10, P = 0.001, P = 0.004, respectively). Pridopidine upregulates expression of BDNF, D1R, GR and AKT/PI3K pathways, known to promote neuronal plasticity and survival, as well as reported to demonstrate therapeutic benefit in HD animal models. Activation of S1R, necessary for its effect on the BDNF pathway, represents a core component of the mode of action of pridopidine. Since the newly identified pathways are downregulated in neurodegenerative diseases, including HD, these findings suggest that pridopidine may exert neuroprotective effects beyond its role in alleviating some symptoms of HD.
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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.