<<< Full experiment listing

PXD015079

PXD015079 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
AnnounceDate2020-02-18
AnnouncementXMLSubmission_2020-05-18_06:00:43.xml
DigitalObjectIdentifierhttp://dx.doi.org/10.6019/PXD015079
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterJuozas Gordevicius
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListOxidation; Acetyl
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-08-19 08:18:55ID requested
12020-02-18 02:22:43announced
22020-05-18 06:00:44announced2020-05-18: Updated publication reference for PubMed record(s): 32151270.
Publication List
Li P, Ensink E, Lang S, Marshall L, Schilthuis M, Lamp J, Vega I, Labrie V, Hemispheric asymmetry in the human brain and in Parkinson's disease is linked to divergent epigenetic patterns in neurons. Genome Biol, 21(1):61(2020) [pubmed]
Keyword List
submitter keyword: autophagy, lysosome, epigenetic, appendix, neurons, Parkinson’s disease
Contact List
Viviane Labrie
contact affiliationCenter for Neurodegenerative Science Van Andel Research Institute 333 Bostwick Ave N.E., Rm 5051 Grand Rapids, MI 49503 Tel: 616-234-5262 ext. 5262 | Email: viviane.labrie@vai.org Lab website: http://labrielab.vai.org/
contact emailviviane.labrie@vai.org
lab head
Juozas Gordevicius
contact affiliationVilnius university
contact emailjuozas.gordevicius@gmc.vu.lt
dataset submitter
Full Dataset Link List
Dataset FTP location
PRIDE project URI
Repository Record List
[ + ]