ArticleActa neuropathologica2021
Altered ceramide metabolism is a feature in the extracellular vesicle-mediated spread of alpha-synuclein in Lewy body disorders.
Article in Acta neuropathologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 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
37 citing papers in PubMed, 62 citations in OpenAlex.
- Lipid Metabolism Reprogramming in the Aging Brain: Glial-Mediated Pathogenic Mechanisms and Translational Strategies in Neurodegeneration.International journal of molecular sciences · 2026Review
- Ceramide-rich extracellular vesicles as pathogenic biomarkers in traumatic brain injury.bioRxiv : the preprint server for biology · 2026Article
- Modest improvement of metabolic and behavioral deficits with long-term ambroxol treatment in a Pink1Acta pharmacologica Sinica · 2026Article
- Glucosylceramide-induced ectosomes propagate pathogenic α-synuclein in Parkinson's disease.Nature cell biology · 2026Article
- Mendelian randomization analysis of 1,400 genetically predicted blood metabolites and ovarian cancer risk.Archives of medical science : AMS · 2026Article
- Adipose-Derived Extracellular Vesicles and Intercellular Crosstalk With Skeletal Muscle: Implications for Sarcopenic Obesity and Metabolic Dysregulation.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026Review
- Neurodegeneration as Ecosystem Failure: A New Paradigm for Prevention and Treatment.International journal of molecular sciences · 2025Review
- p.N370SInternational journal of molecular sciences · 2025Article
- Multiomics analysis to evaluate the enrichment of extracellular vesicles from human plasma.Journal of lipid research · 2025Article
- Elevated hexosylceramides in Parkinson's disease cause gene upregulations in neurons mimicking responses to pathogens.NPJ Parkinson's disease · 2025Article
- The quest for Parkinson's disease biomarkers: traditional and emerging multi-omics approaches.Molecular biology reports · 2025Review
- Cerebrospinal Fluid-Derived Extracellular Vesicles: A Proteomic and Transcriptomic Comparative Analysis of Enrichment Protocols.Journal of extracellular biology · 2025Article
- Lipid metabolism, remodelling and intercellular transfer in the CNS.Nature reviews. Neuroscience · 2025Review
- Extracellular vesicles: new horizons in neurodegeneration.EBioMedicine · 2025Review
- Alpha-synuclein aggregation induces prominent cellular lipid changes as revealed by Raman spectroscopy and machine learning analysis.Brain communications · 2025Article
- Neuronal-enriched small extracellular vesicles trigger a PD-L1-mediated broad suppression of T cells in Parkinson's disease.iScience · 2024Article
- Interaction between α-Synuclein and Bioactive Lipids: Neurodegeneration, Disease Biomarkers and Emerging Therapies.Metabolites · 2024Review
- Recommendations for reproducibility of cerebrospinal fluid extracellular vesicle studies.Journal of extracellular vesicles · 2024Review
- Proteomics and lipidomic analysis reveal dysregulated pathways associated with loss of sacsin.Frontiers in neuroscience · 2024Article
- More than meets the eye in Parkinson's disease and other synucleinopathies: from proteinopathy to lipidopathy.Acta neuropathologica · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
Abstract
Mutations in glucocerebrosidase (GBA) are the most prevalent genetic risk factor for Lewy body disorders (LBD)-collectively Parkinson's disease, Parkinson's disease dementia and dementia with Lewy bodies. Despite this genetic association, it remains unclear how GBA mutations increase susceptibility to develop LBD. We investigated relationships between LBD-specific glucocerebrosidase deficits, GBA-related pathways, and α-synuclein levels in brain tissue from LBD and controls, with and without GBA mutations. We show that LBD is characterised by altered sphingolipid metabolism with prominent elevation of ceramide species, regardless of GBA mutations. Since extracellular vesicles (EV) could be involved in LBD pathogenesis by spreading disease-linked lipids and proteins, we investigated EV derived from post-mortem cerebrospinal fluid (CSF) and brain tissue from GBA mutation carriers and non-carriers. EV purified from LBD CSF and frontal cortex were heavily loaded with ceramides and neurodegeneration-linked proteins including alpha-synuclein and tau. Our in vitro studies demonstrate that LBD EV constitute a "pathological package" capable of inducing aggregation of wild-type alpha-synuclein, mediated through a combination of alpha-synuclein-ceramide interaction and the presence of pathological forms of alpha-synuclein. Together, our findings indicate that abnormalities in ceramide metabolism are a feature of LBD, constituting a promising source of biomarkers, and that GBA mutations likely accelerate the pathological process occurring in sporadic LBD through endolysosomal deficiency.
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.