ArticleParkinson's disease2012
The anticholinesterase phenserine and its enantiomer posiphen as 5'untranslated-region-directed translation blockers of the Parkinson's alpha synuclein expression.
Article in Parkinson's disease, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
What it found
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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
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Anti-seizure Effects and Mechanisms of Berberine: A Systematic Review.Current pharmaceutical biotechnology · 2024Pooled it
- A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with early Alzheimer's Disease.Alzheimer's research & therapy · 2024Trial
- Posiphen as a candidate drug to lower CSF amyloid precursor protein, amyloid-β peptide and τ levels: target engagement, tolerability and pharmacokinetics in humans.Journal of neurology, neurosurgery, and psychiatry · 2012Trial
- Small-Molecule Targeting of the Iron-Responsive Element in the APP mRNA 5'-UTR to Control Amyloid Translation in Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Characterisation of the N-Methyltransferase SgPsmC: Application in the Kinetic Resolution of Pyrroloindolines.Angewandte Chemie (International ed. in English) · 2026Article
- Targeting protein aggregate co-pathologies in neurodegeneration: a viable therapeutic strategy?Molecular neurodegeneration advances · 2026Review
- Pharmacokinetics of Novel Crystalline Buntanetap in Mice, Dogs, and Humans.Biomolecules · 2025Article
- Iron-Mediated Overexpression of Amyloid Precursor Protein via Iron Responsive mRNA in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- α-Synuclein Iron-Responsive-Element RNA and Iron Regulatory Protein Affinity Is Specifically Reduced by Iron in Parkinson's Disease.Biomolecules · 2025Article
- Targeting Iron Responsive Elements (IREs) of APP mRNA into Novel Therapeutics to Control the Translation of Amyloid-β Precursor Protein in Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Small Molecules, α-Synuclein Pathology, and the Search for Effective Treatments in Parkinson's Disease.International journal of molecular sciences · 2024Review
- Novel Therapeutic Horizons:Biomolecules · 2024Review
- A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with Early Alzheimer's Disease.medRxiv : the preprint server for health sciences · 2024Article
- Inhibition of Protein Aggregation and Endoplasmic Reticulum Stress as a Targeted Therapy for α-Synucleinopathy.Pharmaceutics · 2023Review
- The amyloid precursor protein: a converging point in Alzheimer's disease.Molecular neurobiology · 2022Review
- Alpha-Synuclein Aggregation Pathway in Parkinson's Disease: Current Status and Novel Therapeutic Approaches.Cells · 2022Review
- Therapeutics in the Pipeline TargetingPharmacological reviews · 2022Review
- Posiphen Reduces the Levels of Huntingtin Protein through Translation Suppression.Pharmaceutics · 2021Article
- The AKT modulator A-443654 reduces α-synuclein expression and normalizes ER stress and autophagy.The Journal of biological chemistry · 2021Article
- Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
There is compelling support for limiting expression of alpha-synuclein (α-syn) in the brains of Parkinson's disease (PD) patients. An increase of SNCA gene copy number can genetically cause familial PD where increased dose of this pathogenic protein correlates with severity of symptoms (triplication of the SNCA gene causes dementia in PD patients). Gene promoter polymorphisms were shown to increase α-synuclein expression as a risk for PD. Cholinesterase inhibitors can clinically slow cognitive decline in the later stages of PD etiology similar to their widespread use in Alzheimer's disease (AD). Pertinent to this, we identified that the well-tolerated anticholinesterase, phenserine, blocked neural SNCA mRNA translation and tested for targeting via its 5'untranslated region (5'UTR) in a manner similar to its action to limit the expression of the AD-specific amyloid precursor protein (APP). Posiphen, its better-tolerated (+) enantiomer (devoid of anticholinesterase action), repressed neural α-synuclein translation. Primary metabolic analogs of posiphen were, likewise, characterized using primary fetal neurons grown ex vivo from the brains of Parkinson's transgenic mice expressing the human SNCA gene.
Identifiers
What OpenQuestion holds
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.