ArticleJournal of neural transmission (Vienna, Austria : 1996)2011
The alpha-synuclein 5'untranslated region targeted translation blockers: anti-alpha synuclein efficacy of cardiac glycosides and Posiphen.
Article in Journal of neural transmission (Vienna, Austria : 1996), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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.
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Who cites it
51 citing papers in PubMed, 77 citations in OpenAlex.
- 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
- From synaptic development to degeneration: a narrative review of small molecule strategies targeting alpha-synuclein in Parkinson's disease.Metabolic brain disease · 2026Review
- 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
- N-acetyl-l-leucine lowers α-synuclein levels and improves synaptic function in Parkinson's disease models.The Journal of clinical investigation · 2026Article
- Targeting protein aggregate co-pathologies in neurodegeneration: a viable therapeutic strategy?Molecular neurodegeneration advances · 2026Review
- Targeted α-Synuclein mRNA Degradation by PMO-Based RNA-Degrading Chimeras.bioRxiv : the preprint server for biology · 2025Article
- Discovery of Macrocyclic Peptide Binders, Covalent Modifiers, and Degraders of a Structured RNA by mRNA Display.Journal of the American Chemical Society · 2025Article
- Pharmacokinetics of Novel Crystalline Buntanetap in Mice, Dogs, and Humans.Biomolecules · 2025Article
- Review
- Iron-Mediated Overexpression of Amyloid Precursor Protein via Iron Responsive mRNA in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Iron responsive elements mRNA regulate Alzheimer's amyloid precursor protein translation through iron sensing.Frontiers in aging neuroscience · 2025Review
- Novel Therapeutic Horizons:Biomolecules · 2024Review
- Comparative Analysis of Posiphen Pharmacokinetics across Different Species-Similar Absorption and Metabolism in Mouse, Rat, Dog and Human.Biomolecules · 2024Article
- Heterobifunctional small molecules to modulate RNA function.Trends in pharmacological sciences · 2024Review
- The Irony of Iron: The Element with Diverse Influence on Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Detecting ferroptosis and immune infiltration profiles in multiple system atrophy using postmortem brain tissue.Frontiers in neuroscience · 2023Article
- Therapeutics in the Pipeline TargetingPharmacological reviews · 2022Review
- The Compound ATH434 Prevents Alpha-Synuclein Toxicity in a Murine Model of Multiple System Atrophy.Journal of Parkinson's disease · 2022Article
- Posiphen Reduces the Levels of Huntingtin Protein through Translation Suppression.Pharmaceutics · 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
10 authors at 6 institutions in 2 countries.
Funding
Abstract
Increased brain α-synuclein (SNCA) protein expression resulting from gene duplication and triplication can cause a familial form of Parkinson's disease (PD). Dopaminergic neurons exhibit elevated iron levels that can accelerate toxic SNCA fibril formation. Examinations of human post mortem brain have shown that while mRNA levels for SNCA in PD have been shown to be either unchanged or decreased with respect to healthy controls, higher levels of insoluble protein occurs during PD progression. We show evidence that SNCA can be regulated via the 5'untranslated region (5'UTR) of its transcript, which we modeled to fold into a unique RNA stem loop with a CAGUGN apical loop similar to that encoded in the canonical iron-responsive element (IRE) of L- and H-ferritin mRNAs. The SNCA IRE-like stem loop spans the two exons that encode its 5'UTR, whereas, by contrast, the H-ferritin 5'UTR is encoded by a single first exon. We screened a library of 720 natural products (NPs) for their capacity to inhibit SNCA 5'UTR driven luciferase expression. This screen identified several classes of NPs, including the plant cardiac glycosides, mycophenolic acid (an immunosuppressant and Fe chelator), and, additionally, posiphen was identified to repress SNCA 5'UTR conferred translation. Western blotting confirmed that Posiphen and the cardiac glycoside, strophanthidine, selectively blocked SNCA expression (~1 μM IC(50)) in neural cells. For Posiphen this inhibition was accelerated in the presence of iron, thus providing a known APP-directed lead with potential for use as a SNCA blocker for PD therapy. These are candidate drugs with the potential to limit toxic SNCA expression in the brains of PD patients and animal models in vivo.
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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.