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PXD021757

PXD021757 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleEpigenetic inactivation of the autophagy-lysosomal system in the Parkinson’s disease appendix
DescriptionThe gastrointestinal tract may be a site of origin for α-synuclein (α-syn) pathology in idiopathic Parkinson’s disease (PD), and an abundance of aggregated α-syn has recently been demonstrated in both the healthy and PD appendix. However, the molecular changes that enable gut α-syn aggregates to contribute to the development and progression of PD remain unclear. Here, our deep-sequencing of DNA methylation changes at 521 autophagy-lysosomal pathway (ALP) genes in the human appendix and brain in PD and healthy controls indicates a pattern of widespread hypermethylation in the PD appendix that is recapitulated in the PD brain. There is significant overlap in the individual ALP genes affected across the PD appendix and brain, with lysosomal genes specifically downregulated in both regions. Healthy epigenetic aging, which involves a hypermethylation of macroautophagy and selective autophagy genes in the appendix and brain, is disrupted in both areas in PD. In mice, DNA methylation changes at ALP genes induced by chronic gut inflammation are greatly exacerbated by the presence of α-syn pathology. DNA methylation changes at ALP genes induced by α-synucleinopathy are significantly associated with the ALP abnormalities observed in the PD appendix, specifically involving lysosomal genes. Our work, which constitutes an in-depth, unbiased investigation of epigenetic changes in the ALP of the PD gut and brain, identifies the epigenetic misregulation of the ALP, especially a downregulation of lysosomal genes, as a potential culprit for the initiation and spread of α-syn pathology in idiopathic PD.
HostingRepositoryPRIDE
AnnounceDate2021-07-06
AnnouncementXMLSubmission_2021-07-05_21:25:24.263.xml
DigitalObjectIdentifierhttp://dx.doi.org/10.6019/PXD021757
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterJuozas Gordevicius
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-09-30 01:05:47ID requested
12021-07-05 21:25:24announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Autophagy-Lysosomal system, Parkinson's disease, appendix
Contact List
Juozas Gordevicius
contact affiliationBioinformatics Scientist Van Andel Institute
contact emailjuozas.gordevicius@vai.org
lab head
Juozas Gordevicius
contact affiliationVilnius university, Institute of Biotechnology
contact emailjuozas.gordevicius@gmc.vu.lt
dataset submitter
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