PXD011326-3

PXD011326 is an original dataset announced via ProteomeXchange.

Title	An iPSC Model of Early Onset Parkinson's Disease
Description	Early onset Parkinson’s Disease (onset <50 years) accounts for between 10-20 percent of all patients. While some of these cases are associated with specific mutations, the majority are sporadic where the cause is unknown. We generated induced pluripotent stem cells from sporadic early onset patients and differentiated them to dopamine neurons. At early stages in culture (30 days) we found significant elevations in soluble α-synuclein protein levels when compared to controls. This was associated with reductions in lysosomal membrane proteins such as LAMP1 and an increase in phosphorylated protein kinase C-α (p-PKCα). Testing activators of lysosomal function showed that specific phorbal esters reduced both α-synuclein and p-PKCα levels and increased LAMP1 expression. Interestingly, very low doses of the drug PEP005 were able to reduce α-synuclein levels without affecting p-PKCα. Similar effects of PEP005 on α-synuclein expression were seen following infusion into the mouse brain. Our data show that early onset sporadic Parkinson’s Disease can be accurately predicted using a ratio of α-synuclein and p-PKCα in dopamine neural cultures derived from patient iPSC’s and that specific phorbal esters can alter both biomarkers making these drugs promising candidates to treat Parkinson’s Disease.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:49:17.232.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Victoria Dardov
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	TripleTOF 6600

Revision	Datetime	Status	ChangeLog Entry
0	2018-10-10 02:39:07	ID requested
1	2019-12-06 10:26:42	announced
2	2020-06-18 03:24:37	announced	2020-06-18: Updated publication reference for PubMed record(s): 31988461.
⏵ 3	2024-10-22 04:49:25	announced	2024-10-22: Updated project metadata.

10.1038/s41591-019-0739-1;

Laperle AH, Sances S, Yucer N, Dardov VJ, Garcia VJ, Ho R, Fulton AN, Jones MR, Roxas KM, Avalos P, West D, Banuelos MG, Shu Z, Murali R, Maidment NT, Van Eyk JE, Tagliati M, Svendsen CN, iPSC modeling of young-onset Parkinson's disease reveals a molecular signature of disease and novel therapeutic candidates. Nat Med, 26(2):289-299(2020) [pubmed]

curator keyword: Biomedical

submitter keyword: Human, Parkinson's Disease, iPSC

Jennifer Van Eyk
contact affiliation	Cedars Sinai Medical Center
contact email	jennifer.vaneyk@cshs.org
lab head
Victoria Dardov
contact affiliation	Cedars Sinai Medical Center
contact email	victoria.dardov@cshs.org
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2019/12/PXD011326

PRIDE project URI

• PRIDE
  1. PXD011326
     1. Label: PRIDE project
     2. Name: An iPSC Model of Early Onset Parkinson's Disease