PXD000866

PXD000866 is an original dataset announced via ProteomeXchange.

Title	iPSC-derived neurons from GBA1-associated Parkinson's disease patients show autophagic/lysosomal dysfunction and impaired calcium homeostasis
Description	Mutations in the acid β-glucocerebrosidase (GBA1) gene, responsible for the lysosomal storage disorder Gaucher’s disease (GD), are the strongest genetic risk factor for Parkinson’s disease (PD) known to date. To elucidate the mechanisms underlying neurodegeneration in these patients, we generated induced pluripotent stem cells from subjects with GD and PD harboring GBA1 mutations and differentiated them to midbrain dopaminergic neurons. Highly enriched neurons showed a reduction of glucocerebrosidase activity and protein levels, increased glucosylceramide and α-synuclein levels and autophagic/lysosomal defects. Quantitative proteomics profiling revealed an increase of the neuronal calcium-binding protein 2 (NECAB2) in diseased neurons. We found dysregulation of calcium homeostasis and increased vulnerability to stress responses involving elevation of cytosolic calcium in mutant neurons. Importantly, correction of the mutations rescued such pathological phenotypes. Our findings provide evidence for a link between GBA1 mutations and complex changes in autophagic/lysosomal system and intracellular calcium homeostasis, which underlie vulnerability to neurodegeneration.
HostingRepository	PRIDE
AnnounceDate	2014-07-24
AnnouncementXML	Submission_2014-07-24_05:17:07.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fiona McAllister
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2014-04-01 05:27:02	ID requested
1	2014-06-03 03:58:35	announced
2	2014-06-16 01:25:06	announced	Updated publication reference for PubMed record(s): 24905578.
⏵ 3	2014-07-24 05:17:07	announced	Updated project metadata.

Sch, ö, ndorf DC, Aureli M, McAllister FE, Hindley CJ, Mayer F, Schmid B, Sardi SP, Valsecchi M, Hoffmann S, Schwarz LK, Hedrich U, Berg D, Shihabuddin LS, Hu J, Pruszak J, Gygi SP, Sonnino S, Gasser T, Deleidi M, iPSC-derived neurons from GBA1-associated Parkinson's disease patients show autophagic defects and impaired calcium homeostasis. Nat Commun, 5():4028(2014) [pubmed]

curator keyword: Biomedical

submitter keyword: Neurons, human, TMT

Michela Deleidi
contact affiliation	Dept. for Neurodegenerative Diseases, German Center for Neurodegenerative Diseases, Tubingen, Germany
contact email	michela.deleidi@dzne.de
lab head
Fiona McAllister
contact affiliation	Stanford
contact email	fionaemca@gmail.com
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/2014/06/PXD000866

PRIDE project URI

• PRIDE
  1. PXD000866
     1. Label: PRIDE project
     2. Name: iPSC-derived neurons from GBA1-associated Parkinson's disease patients show autophagic/lysosomal dysfunction and impaired calcium homeostasis