PXD015079-1

PXD015079 is an original dataset announced via ProteomeXchange.

Title	Epigenetic inactivation of the autophagy-lysosomal system in the Parkinson’s disease appendix
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2020-02-18
AnnouncementXML	Submission_2020-02-18_02:22:42.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD015079
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Juozas Gordevicius
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	Oxidation; Acetyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-08-19 08:18:55	ID requested
⏵ 1	2020-02-18 02:22:43	announced
2	2020-05-18 06:00:44	announced	2020-05-18: Updated publication reference for PubMed record(s): 32151270.

Dataset with its publication pending

submitter keyword: autophagy, lysosome, epigenetic, appendix, neurons, Parkinson’s disease

Viviane Labrie
contact affiliation	Center 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 email	viviane.labrie@vai.org
lab head
Juozas Gordevicius
contact affiliation	Vilnius university
contact email	juozas.gordevicius@gmc.vu.lt
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD015079
     1. Label: PRIDE project
     2. Name: Epigenetic inactivation of the autophagy-lysosomal system in the Parkinson’s disease appendix