PXD020046

PXD020046 is an original dataset announced via ProteomeXchange.

Title	Cysteamine-bicalutamide combination therapy restores α-ketoglutarate and corrects proximal tubule phenotype in nephropathic cystinosis
Description	Nephropathic cystinosis is a severe monogenetic kidney disorder caused by mutations in CTNS, encoding the lysosomal transporter cystinosin, resulting in lysosomal cystine accumulation. The sole treatment, cysteamine, slows down the disease progression, but does not correct the established proximal tubulopathy. Here, we developed a new therapeutic strategy by applying an omics-based strategy to expand our knowledge on the complexity of the disease and prioritize drug targets in cystinosis. We identified alpha-ketoglutarate as a key metabolite linking cystinosin loss, lysosomal autophagy defect and proximal tubular impairment in cystinosis. This insight offered a bicalutamide-cysteamine combination treatment as a novel dual target pharmacological approach for the phenotypical correction of cystinotic proximal tubule cells, patient-derived kidney tubuloids and cystinotic zebrafish.
HostingRepository	PRIDE
AnnounceDate	2021-06-16
AnnouncementXML	Submission_2021-06-16_08:10:23.840.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Charlotte van Gelder
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-26 04:18:51	ID requested
⏵ 1	2021-06-16 08:10:24	announced

Dataset with its publication pending

submitter keyword: Cystinosis, CRISPR/Cas9, alpha-ketoglutarate, Autophagy, Renal Fanconi syndrome, CysteamineBicalutamide combination therapy

Prof. Dr. Maarten Altelaar
contact affiliation	Professor
contact email	m.altelaar@uu.nl
lab head
Charlotte van Gelder
contact affiliation	Utrecht University
contact email	c.a.g.h.vangelder@uu.nl
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/2021/06/PXD020046

PRIDE project URI

• PRIDE
  1. PXD020046
     1. Label: PRIDE project
     2. Name: Cysteamine-bicalutamide combination therapy restores α-ketoglutarate and corrects proximal tubule phenotype in nephropathic cystinosis