<<< Full experiment listing

PXD011326

PXD011326 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAn iPSC Model of Early Onset Parkinson's Disease
DescriptionEarly 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.
HostingRepositoryPRIDE
AnnounceDate2019-12-06
AnnouncementXMLSubmission_2020-06-18_03:24:36.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterVictoria Dardov
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentTripleTOF 6600
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-10-10 02:39:07ID requested
12019-12-06 10:26:42announced
22020-06-18 03:24:37announced2020-06-18: Updated publication reference for PubMed record(s): 31988461.
Publication List
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]
Keyword List
curator keyword: Biomedical
submitter keyword: Human, iPSC, Parkinson's Disease
Contact List
Jennifer Van Eyk
contact affiliationCedars Sinai Medical Center
contact emailjennifer.vaneyk@cshs.org
lab head
Victoria Dardov
contact affiliationCedars Sinai Medical Center
contact emailvictoria.dardov@cshs.org
dataset submitter
Full Dataset Link List
Dataset FTP location
PRIDE project URI
Repository Record List
[ + ]