Evidence map›Paper›PMID 41680444›Full record

ArticleNature cell biology2026

Glucosylceramide-induced ectosomes propagate pathogenic α-synuclein in Parkinson's disease.

Julie Jacquemyn, Brian Marriott, Jinlan Chang, Ehlam Iftikhar, Kennedi Chik, Nathanael Y J Lee, Luis F Rubio Atonal, Ceili Green, Jeremy Wong, Claudia Acevedo-Morantes and 8 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature cell biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Julie JacquemynDepartment of Physiology, University of Alberta, Edmonton, Alberta, Canada.
Brian MarriottDepartment of Physiology, University of Alberta, Edmonton, Alberta, Canada.
Jinlan ChangDepartment of Physiology, University of Alberta, Edmonton, Alberta, Canada.
Ehlam IftikharDepartment of Physiology, University of Alberta, Edmonton, Alberta, Canada.ORCID http://orcid.org/0009-0009-0420-2340
Kennedi ChikDepartment of Physiology, University of Alberta, Edmonton, Alberta, Canada.
Nathanael Y J LeeDepartment of Physiology, University of Alberta, Edmonton, Alberta, Canada.
Luis F Rubio AtonalDepartment of Physiology, University of Alberta, Edmonton, Alberta, Canada.
Ceili GreenDepartment of Physiology, University of Alberta, Edmonton, Alberta, Canada.
Jeremy WongDepartment of Physiology, University of Alberta, Edmonton, Alberta, Canada.ORCID http://orcid.org/0009-0006-1010-1114
Claudia Acevedo-MorantesDepartment of Physiology, University of Alberta, Edmonton, Alberta, Canada.
Carol X-Q ChenThe Neuro's Early Drug Discovery Unit, McGill University, Montreal, Quebec, Canada.
Michael NicouleauThe Neuro's Early Drug Discovery Unit, McGill University, Montreal, Quebec, Canada.
Zhipeng YouThe Neuro's Early Drug Discovery Unit, McGill University, Montreal, Quebec, Canada.
Eric DeneaultThe Neuro's Early Drug Discovery Unit, McGill University, Montreal, Quebec, Canada.
Narges AbdianThe Neuro's Early Drug Discovery Unit, McGill University, Montreal, Quebec, Canada.
Thomas M DurcanThe Neuro's Early Drug Discovery Unit, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0003-3942-1956
Jesse JacksonDepartment of Physiology, University of Alberta, Edmonton, Alberta, Canada.
Maria S IoannouDepartment of Physiology, University of Alberta, Edmonton, Alberta, Canada. ioannou@ualberta.ca.ORCID http://orcid.org/0000-0001-6252-8626

Funding

Fondation Brain Canada (Fondation Neuro Canada) #5946Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) #191990
6 · The paper itself

Abstract

The intercellular transmission of α-synuclein contributes to Parkinson's disease pathology. Yet, the mechanisms of α-synuclein spread are not fully understood. Here we used live-cell microscopy to examine the impact of Parkinson's disease associated lipid alterations on α-synuclein release. We discovered that increased glucosylceramides as a consequence of reduced β-glucocerebrosidase activity induce ectosome shedding from primary neurons and from dopaminergic neurons derived from induced pluripotent stem cells of a patient with Parkinson's disease harbouring mutations in GBA1 (N370S, L444P and W378G) and LRRK2 (G2019S and R1441H) compared with their isogenic control. We show that elevated glucosylceramide and the pharmacological inhibition of β-glucocerebrosidase similarly increase vesicle release and uptake by other neurons in mouse brains. Finally, we show that ectosomes are loaded with α-synuclein and lead to the transmission of α-synuclein pathology to neighbouring neurons. These data reveal ectosomes as a major route for α-synuclein transmission in Parkinson's disease.

Indexed as

alpha-SynucleinDopaminergic NeuronsGlucosylceramidesParkinson DiseaseAnimalsCells, CulturedGlucosylceramidaseHumansInduced Pluripotent Stem CellsLeucine-Rich Repeat Serine-Threonine Protein Kinase-2MaleMiceMice, Inbred C57BLMutationProtein Serine-Threonine Kinasesalpha-SynucleinGBA protein, humanGlucosylceramidaseGlucosylceramidesLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LRRK2 protein, humanProtein Serine-Threonine Kinases

Identifiers

PMID41680444

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.