PXD030831

PXD030831 is an original dataset announced via ProteomeXchange.

Title	Cortical pathology in Vanishing white matter
Description	Vanishing white matter (VWM) is classified as a leukodystrophy with astrocytes as primary drivers in its pathogenesis. Magnetic resonance imaging has documented the progressive thinning of cortices in long-surviving patients. Routine histopathological analyses, however, have not yet pointed to cortical involvement in VWM. Here, we provide a comprehensive analysis of the VWM cortex. We employed high-resolution-mass-spectrometry-based proteomics and immunohistochemistry to gain insight into possible molecular disease mechanisms in the cortices of VWM patients. The proteome analysis revealed 268 differentially expressed proteins in the VWM cortices compared to the controls. A majority of these proteins formed a major protein interaction network. A subsequent gene ontology analysis identified enrichment for terms such as cellular metabolism, particularly mitochondrial activity. Importantly, some of the proteins with the most prominent changes in expression were found in astrocytes, indicating cortical astrocytic involvement. Indeed, we confirmed that VWM cortical astrocytes exhibit morphological changes and are less complex in structure than control cells. Our findings also suggest that these astrocytes are immature and not reactive. Taken together, we provide insights into cortical involvement in VWM, which has to be taken into account when developing therapeutic strategies.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:54:28.597.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jodie Man
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-08 03:01:07	ID requested
1	2023-01-04 03:35:44	announced
⏵ 2	2023-11-14 08:54:29	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: Human, LC-MSMS, brain, Astrocytes, vanishing white matter, leukodystrophy

Marianna Bugiani
contact affiliation	Department of Pathology, Amsterdam University Medical Centres, Vrije Universiteit Amsterdam and Amsterdam Neuroscience, Amsterdam, The Netherlands
contact email	m.bugiani@amsterdamumc.nl
lab head
Jodie Man
contact affiliation	Amsterdam UMC - Location VUMc
contact email	j.man@amsterdamumc.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/2023/01/PXD030831

PRIDE project URI

• PRIDE
  1. PXD030831
     1. Label: PRIDE project
     2. Name: Cortical pathology in Vanishing white matter