ArticleNeuron2018
Reversible Conformational Conversion of α-Synuclein into Toxic Assemblies by Glucosylceramide.
Article in Neuron, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05287503 (Ambroxol as a Disease-modifying Treatment to Reduce the Risk of Cognitive Impairment in GBA-associated Parkinson's Disease. A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Trial), which is not on this map. Cited by 147 papers.
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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.
Ambroxol as a Disease-modifying Treatment to Reduce the Risk of Cognitive Impairment in GBA-associated Parkinson's Disease. A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Trial
Who cites it
147 citing papers in PubMed, 226 citations in OpenAlex.
- Safety, Pharmacokinetics, and Pharmacodynamics of Oral Venglustat in Patients with Parkinson's Disease and a GBA Mutation: Results from Part 1 of the Randomized, Double-Blinded, Placebo-Controlled MOVES-PD Trial.Journal of Parkinson's disease · 2022Trial
- Article
- Review
- Modest improvement of metabolic and behavioral deficits with long-term ambroxol treatment in a Pink1Acta pharmacologica Sinica · 2026Article
- Age at onset of Parkinson's disease modulates the sphingolipid-dopaminergic interplay in autonomic progression.NPJ Parkinson's disease · 2026Article
- Ectosomes step forward in α-synuclein spread.Nature cell biology · 2026Article
- Glucosylceramide-induced ectosomes propagate pathogenic α-synuclein in Parkinson's disease.Nature cell biology · 2026Article
- Multi-omics insights into GBA1-associated Parkinson's disease: interplay of genomics, transcriptomics, proteomics, and lipidomics.Molecular neurodegeneration · 2026Review
- Glucosylceramides trigger the shedding of alpha-synuclein laden ectosomes.Extracellular vesicles and circulating nucleic acids · 2026Article
- Refining Mouse Models of Gaucher Disease: Advancing Mechanistic Insights, Biomarker Discovery, and Therapeutic Strategies.International journal of molecular sciences · 2025Review
- A pathogenic alpha synuclein variant exacerbates disease progression in a neuron-specific Gba-KO mouse.Neurobiology of disease · 2025Article
- Synaptic vesicle endocytosis deficits underlie cognitive dysfunction in mouse models of GBA-linked Parkinson's disease and dementia with Lewy bodies.Nature communications · 2025Article
- Elevated hexosylceramides in Parkinson's disease cause gene upregulations in neurons mimicking responses to pathogens.NPJ Parkinson's disease · 2025Article
- Recombinant cathepsins B and L promote α-synuclein clearance and restore lysosomal function in human and murine models with α-synuclein pathology.Molecular neurodegeneration · 2025Article
- Determination of bioactive profile of Polygala vulgaris L. by GC-MS and molecular docking.BMC chemistry · 2025Article
- Lewy body dementia: exploring biomarkers and pathogenic interactions of amyloid β, tau, and α-synuclein.Molecular neurodegeneration · 2025Review
- Bidirectional regulation of glycoprotein nonmetastatic melanoma protein B by β-glucocerebrosidase deficiency inbioRxiv : the preprint server for biology · 2025Article
- A mechanistic model of pure and lipidic α-synuclein aggregation for advancing Parkinson's therapies.Communications chemistry · 2025Article
- Linear ubiquitination at damaged lysosomes induces local NFKB activation and controls cell survival.Autophagy · 2025Article
- Cerebrospinal ceramides and cognition as a function of striatal asymmetry in early stage of Parkinson's disease.Journal of Parkinson's disease · 2025Article
87 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
α-Synuclein (α-syn) aggregation is a key event in Parkinson's disease (PD). Mutations in glycosphingolipid (GSL)-degrading glucocerebrosidase are risk factors for PD, indicating that disrupted GSL clearance plays a key role in α-syn aggregation. However, the mechanisms of GSL-induced aggregation are not completely understood. We document the presence of physiological α-syn conformers in human midbrain dopamine neurons and tested their contribution to the aggregation process. Pathological α-syn assembly mainly occurred through the conversion of high molecular weight (HMW) physiological α-syn conformers into compact, assembly-state intermediates by glucosylceramide (GluCer), without apparent disassembly into free monomers. This process was reversible in vitro through GluCer depletion. Reducing GSLs in PD patient neurons with and without GBA1 mutations diminished pathology and restored physiological α-syn conformers that associated with synapses. Our work indicates that GSLs control the toxic conversion of physiological α-syn conformers in a reversible manner that is amenable to therapeutic intervention by GSL reducing agents.
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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.