ArticlePloS one2016
An Anti-Parkinson's Disease Drug via Targeting Adenosine A2A Receptor Enhances Amyloid-β Generation and γ-Secretase Activity.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- The potential role of adenosinergic pathway and methylxanthines in Parkinson's disease: Blowing in the wind or not.Purinergic signalling · 2026Review
- γ-secretase facilitates retromer-mediated retrograde transport.Journal of cell science · 2025Article
- γ-secretase facilitates retromer-mediated retrograde transport.bioRxiv : the preprint server for biology · 2024Article
- The multifaceted functions of β-arrestins and their therapeutic potential in neurodegenerative diseases.Experimental & molecular medicine · 2024Review
- Bidirectional Control between Cholesterol Shuttle and Purine Signal at the Central Nervous System.International journal of molecular sciences · 2022Review
- Separation and identification of an impurity from the istradefylline intermediate.RSC advances · 2020Article
- Potential therapeutic effects of antagonizing adenosine AMolecular and cellular biochemistry · 2020Article
- Beneficial Effect of a Selective Adenosine AFrontiers in molecular neuroscience · 2018Article
- The Adenosinergic Signaling: A Complex but Promising Therapeutic Target for Alzheimer's Disease.Frontiers in neuroscience · 2018Review
- A tricyclic antidepressant, amoxapine, reduces amyloid-β generation through multiple serotonin receptor 6-mediated targets.Scientific reports · 2017Article
- Article
- Review
- Purinergic Signalling: Therapeutic Developments.Frontiers in pharmacology · 2017Review
- Purinergic Receptors of the Central Nervous System: Biology, PET Ligands, and Their Applications.Molecular imagingReview
- Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
γ-secretase mediates the intramembranous proteolysis of amyloid precursor protein (APP) and determines the generation of Aβ which is associated with Alzheimer's disease (AD). Here we identified that an anti-Parkinson's disease drug, Istradefylline, could enhance Aβ generation in various cell lines and primary neuronal cells of APP/PS1 mouse. Moreover, the increased generation of Aβ42 was detected in the cortex of APP/PS1 mouse after chronic treatment with Istradefylline. Istradefylline promoted the activity of γ-secretase which could lead to increased Aβ production. These effects of Istradefylline were reduced by the knockdown of A2AR but independent of A2AR-mediated G protein- or β-arrestin-dependent signal pathway. We further observed that A2AR colocalized with γ-secretase in endosomes and physically interacted with the catalytic subunit presenilin-1 (PS1). Interestingly, Istradefylline attenuated the interaction in time- and dosage-dependent manners. Moreover the knockdown of A2AR which in theory would release PS1 potentiated both Aβ generation and γ-secretase activity. Thus, our study implies that the association of A2AR could modulate γ-secretase activity. Istradefylline enhance Aβ generation and γ-secretase activity possibly via modulating the interaction between A2AR and γ-secretase, which may bring some undesired effects in the central nervous system (CNS).
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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.