ArticleNPJ Parkinson's disease2020
Comparative proteomic analysis highlights metabolic dysfunction in α-synucleinopathy.
Article in NPJ Parkinson's disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 29 citations in OpenAlex.
- A Degron Decoy System Co-opts Pathological Seeding to Enable Clearance of Multimeric α-Synuclein.bioRxiv : the preprint server for biology · 2026Article
- Glycerol 3-phosphate acyltransferase exacerbates α-synuclein-induced toxicity by increasing lipid peroxidation.Nature communications · 2026Article
- In vivo and in silico models of Drosophila for Parkinson's disease.The FEBS journal · 2025Review
- Intersecting impact of CAG repeat and huntingtin knockout in stem cell-derived cortical neurons.Neurobiology of disease · 2025Article
- An integrative systems-biology approach defines mechanisms of Alzheimer's disease neurodegeneration.Nature communications · 2025Article
- Longitudinal multi-omics in alpha-synuclein Drosophila model discriminates disease- from age-associated pathologies in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- Biotin mitigates the development of manganese-induced, Parkinson's disease-related neurotoxicity inScience signaling · 2025Article
- Mass spectrometry-based proteomics for biomarker discovery in theNeuroprotection (Chichester, England) · 2024Review
- Comparative Proteomics Highlights that GenX Exposure Leads to Metabolic Defects and Inflammation in Astrocytes.Environmental science & technology · 2024Article
- Transcriptional programs mediating neuronal toxicity and altered glial-neuronal signaling in aGenome research · 2024Article
- Transcriptional programs mediating neuronal toxicity and altered glial-neuronal signaling in abioRxiv : the preprint server for biology · 2024Article
- Origins of nervous tissue susceptibility to ferroptosis.Cell insight · 2023Review
- Crucial neuroprotective roles of the metabolite BH4 in dopaminergic neurons.bioRxiv : the preprint server for biology · 2023Article
- α-Synuclein Promotes Neuronal Dysfunction and Death by Disrupting the Binding of Ankyrin to β-Spectrin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- UPLC-Q-TOF/MS Based Plasma Metabolomics for Identification of Paeonol's Metabolic Target in Endometriosis.Molecules (Basel, Switzerland) · 2023Article
- Microglial ion channels: Key players in non-cell autonomous neurodegeneration.Neurobiology of disease · 2022Review
- Intestine-derived α-synuclein initiates and aggravates pathogenesis of Parkinson's disease in Drosophila.Translational neurodegeneration · 2022Article
- Lipotoxicity Downstream of α-Synuclein Imbalance: A Relevant Pathomechanism in Synucleinopathies?Biomolecules · 2021Review
- Parkinson's disease risk genes act in glia to control neuronal α-synuclein toxicity.Neurobiology of disease · 2021Article
- Precision Medicine on the Fly: Using Drosophila to Decipher Gene-Environment Interactions in Parkinson's Disease.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
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 3 institutions in 1 country.
Funding
Abstract
The synaptic protein α-synuclein is linked through genetics and neuropathology to the pathogenesis of Parkinson's disease and related disorders. However, the mechanisms by which α-synuclein influences disease onset and progression are incompletely understood. To identify pathogenic pathways and therapeutic targets we performed proteomic analysis in a highly penetrant new Drosophila model of α-synucleinopathy. We identified 476 significantly upregulated and 563 significantly downregulated proteins in heads from α-synucleinopathy model flies compared to controls. We then used multiple complementary analyses to identify and prioritize genes and pathways within the large set of differentially expressed proteins for functional studies. We performed Gene Ontology enrichment analysis, integrated our proteomic changes with human Parkinson's disease genetic studies, and compared the α-synucleinopathy proteome with that of tauopathy model flies, which are relevant to Alzheimer's disease and related disorders. These approaches identified GTP cyclohydrolase (GCH1) and folate metabolism as candidate mediators of α-synuclein neurotoxicity. In functional validation studies, we found that the knockdown of Drosophila Gch1 enhanced locomotor deficits in α-synuclein transgenic flies, while folate supplementation protected from α-synuclein toxicity. Our integrative analysis suggested that mitochondrial dysfunction was a common downstream mediator of neurodegeneration. Accordingly, Gch1 knockdown enhanced metabolic dysfunction in α-synuclein transgenic fly brains while folate supplementation partially normalized brain bioenergetics. Here we outline and implement an integrative approach to identify and validate potential therapeutic pathways using comparative proteomics and genetics and capitalizing on the facile genetic and pharmacological tools available in Drosophila.
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.