Parkinson's disease-associated <i>PINK1</i> loss disrupts ensheathing glia and causes dopaminergic neuron synapse loss.
Overview
- VIB-KU Leuven Center for Neuroscience, Leuven, Belgium
- KU Leuven, Department of Neurosciences, Leuven Brain Institute, Leuven, Belgium
- VIB-KU Leuven Center for Neuroscience, Single Cell and Microfluidics Expertise Unit, Leuven, Belgium
- VIB-KU Leuven Center for Neuroscience, Single Cell Bioinformatics Unit, Leuven, Belgium
- VIB Flow Core Leuven, VIB Technologies, Leuven, Belgium
- Medical University of Innsbruck, Institute of Human Genetics, Innsbruck, Austria
Abstract
Parkinson’s disease (PD) is commonly associated with the loss of dopaminergic neurons in the substantia nigra, but many other cell types are affected even before neuron loss occurs. Recent studies have linked oligodendrocytes to early stages of PD, though their precise role is still unclear. PINK1 is mutated in familial PD, and through unbiased single-cell sequencing of the entire brain of Drosophila Pink1 models, we observed significant gene deregulation in ensheathing glia (EG), cells that share functional similarities with oligodendrocytes. We found that the loss of Pink1 leads to abnormalities in EG, similar to the reactive response of EG seen upon nerve injury. Using cell-type-specific transcriptomics, we identified deregulated genes in EG as potential functional modifiers. Specifically downregulating two trafficking factors in EG, Vps35 and Vps13, also mutated in PD, was sufficient to rescue neuronal function and protect against dopaminergic synapse loss. Our findings demonstrate that Pink1 loss in neurons triggers an injury-like response in EG, and that Pink1 loss in EG, in turn, disrupts neuronal function. Vesicle trafficking components, which may regulate membrane interactions between organelles in EG, seem to play a role in maintaining neuronal health and ultimately preventing dopaminergic synapse loss. Our work highlights the essential role of glial support cells in the pathogenesis of PD and identifies vesicle trafficking within these cells in disease progression.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
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Data
Datasets cited
- geo:GSE322929, at NCBI GEO; found in “Data availability”
Data availability
RNA sequence data were deposited in GEO (accession number GSE322929 (https://
The following dataset was generated:
Ghezzi L, Kuenen S, Pech U, Schoovaerts N, Kilic A, Poovathingal S, Davie K, Lamote J, Praschberger R, Verstreken P. 2026. Parkinson's Disease-Associated Pink1 Loss Disrupts Ensheathing Glia And Causes Dopaminergic Neuron Synapse Loss. NCBI Gene Expression Omnibus. GSE322929
The following previously published dataset was used:
Janssens J, Pech U, Aerts S, Verstreken P. 2025. Rescuing early Parkinson-induced hyposmia prevents dopaminergic system failure [fruit fly] NCBI Gene Expression Omnibus. GSE228843
Reproduced under the paper's license (CC BY), from the paper cited above.
Materials availability
Data, code, Drosophila models, and reagents are available upon request.
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, pages, dates, 10 authors, 1 keyword, 11 MeSH terms, 2 funders, 71 references, 13 RRIDs.
Cite
This paper
Ghezzi, L., Kuenen, S., Pech, U., Schoovaerts, N., Kilic, A., Poovathingal, S., Davie, K., Lamote, J., Praschberger, R., & Verstreken, P. (2026). Parkinson's disease-associated &
BibTeX
@article{ghezzi2026parki
author = {Ghezzi, Lorenzo and Kuenen, Sabine and Pech, Ulrike and Schoovaerts, Nils and Kilic, Ayse and Poovathingal, Suresh and Davie, Kristofer and Lamote, Jochen and Praschberger, Roman and Verstreken, Patrik},
title = {{Parkinson's disease-associated \&
journal = {eLife},
year = {2026},
month = aug,
volume = {14},
pages = {RP105386},
publisher = {eLife Sciences Publications, Ltd},
issn = {2050-084X},
doi = {10.7554/
url = {https://
pmid = {42592915},
pmcid = {PMC13472629}
}
RIS
TY - JOUR
AU - Ghezzi, Lorenzo
AU - Kuenen, Sabine
AU - Pech, Ulrike
AU - Schoovaerts, Nils
AU - Kilic, Ayse
AU - Poovathingal, Suresh
AU - Davie, Kristofer
AU - Lamote, Jochen
AU - Praschberger, Roman
AU - Verstreken, Patrik
TI - Parkinson's disease-associated &
T2 - eLife
J2 - Elife
PY - 2026
DA - 2026/
VL - 14
SP - RP105386
SN - 2050-084X
PB - eLife Sciences Publications, Ltd
DO - 10.7554/
UR - https://
LA - en
ER -
CSL-JSON
{
"id": "10.7554/
"type": "article-journal",
"title": "Parkinson's disease-associated &
"container-title": "eLife",
"author": [
{
"family": "Ghezzi",
"given": "Lorenzo"
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"family": "Kuenen",
"given": "Sabine"
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{
"family": "Pech",
"given": "Ulrike"
},
{
"family": "Schoovaerts",
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"family": "Kilic",
"given": "Ayse"
},
{
"family": "Poovathingal",
"given": "Suresh"
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"given": "Kristofer"
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"family": "Lamote",
"given": "Jochen"
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"given": "Roman"
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{
"family": "Verstreken",
"given": "Patrik"
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"DOI": "10.7554/
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"publisher": "eLife Sciences Publications, Ltd",
"URL": "https://
"language": "en",
"issued": {
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