ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
The stimulation of adenosine A2A receptors ameliorates the pathological phenotype of fibroblasts from Niemann-Pick type C patients.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
19 citing papers in PubMed, 38 citations in OpenAlex.
- AMetabolites · 2026Article
- Impaired mitochondria-initiated crosstalk with lysosomes reciprocally aggravates mitochondrial defect through LManVI.Nature communications · 2025Article
- Neuronal A2A receptor exacerbates synapse loss and memory deficits in APP/PS1 mice.Brain : a journal of neurology · 2024Article
- Article
- Adenosine AFrontiers in pharmacology · 2024Article
- Adenosine ACurrent issues in molecular biology · 2023Article
- Bidirectional Control between Cholesterol Shuttle and Purine Signal at the Central Nervous System.International journal of molecular sciences · 2022Review
- Repurposing Dipyridamole in Niemann Pick Type C Disease: A Proof of Concept Study.International journal of molecular sciences · 2022Article
- Article
- The Future of Genetic Disease Studies: Assembling an Updated Multidisciplinary Toolbox.Frontiers in cell and developmental biology · 2022Article
- Myelin Defects in Niemann-Pick Type C Disease: Mechanisms and Possible Therapeutic Perspectives.International journal of molecular sciences · 2021Review
- The lysosome: A potential juncture between SARS-CoV-2 infectivity and Niemann-Pick disease type C, with therapeutic implications.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Lysosomal CaCold Spring Harbor perspectives in biology · 2020Review
- Adenosine AScientific reports · 2019Article
- Membrane cholesterol depletion reduces downstream signaling activity of the adenosine ABiochimica et biophysica acta. Biomembranes · 2019Article
- Neuronal adenosine APurinergic signalling · 2018Article
- Lysosomal and Mitochondrial Liaisons in Niemann-Pick Disease.Frontiers in physiology · 2017Review
- Acidic CaMessenger (Los Angeles, Calif. : Print) · 2016Article
- Preferential Coupling of the NAADP Pathway to Exocytosis in T-Cells.Messenger (Los Angeles, Calif. : Print) · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Niemann-Pick type C1 (NPC1) disease is a rare neurovisceral disorder characterized by intracellular accumulation of unesterified cholesterol, sphingolipids, and other lipids in the lysosomal compartment. A deregulation of lysosomal calcium has been identified as one of the earliest steps of the degenerative process. Since adenosine A2A receptors (A2ARs) control lysosome trafficking and pH, which closely regulates lysosomal calcium, we hypothesized a role for these receptors in NPC1. The aim of this study was to evaluate the effects of the A2AR agonist CGS21680 on human control and NPC1 fibroblasts. We show that CGS21680 raises lysosomal calcium levels and rescues mitochondrial functionality (mitochondrial inner membrane potential and expression of the complex IV of the mitochondrial respiratory chain), which is compromised in NPC1 cells. These effects are prevented by the selective blockade of A2ARs by the antagonist ZM241385. The effects of A2AR activation on lysosomal calcium are not mediated by the cAMP/PKA pathway but they appear to involve the phosphorylation of ERK1/2. Finally, CGS21680 reduces cholesterol accumulation (Filipin III staining), which is the main criterion currently used for identification of a compound or pathway that would be beneficial for NPC disease, and such an effect is prevented by the Ca(2+) chelator BAPTA-AM. Our findings strongly support the hypothesis that A2AR agonists may represent a therapeutic option for NPC1 and provide insights on their mechanisms of action.
Indexed as
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.