PXD040861-1

PXD040861 is an original dataset announced via ProteomeXchange.

Title	Regional vulnerability of brain white matter in VWM
Description	Vanishing white matter (VWM) is a leukodystrophy that primarily manifests in young children. In this disease, the brain white matter is differentially affected in a predictable pattern with telencephalic brain areas being more severely affected, while others remain allegedly completely spared. Using high-resolution mass spectrometry-based proteomics, we investigated the proteome patterns of the severely affected white matter in the frontal lobe and normal appearing pons in VWM and control cases to identify molecular bases underlying regional vulnerability. By comparing VWM patients to controls, we identified disease-specific proteome patterns. We showed substantial pathogenic changes in both the frontal white matter and pons at the protein level. Side-by-side comparison of brain region-specific proteome patterns further revealed regional differences. We found that different cell types are affected in the VWM frontal white matter than in the pons. Gene ontology and pathway analyses identified involvement of region distinct biological processes, of which pathways implicated in cellular respiratory metabolism were overarching features. In the VWM frontal white matter, proteome changes were associated with decrease in glycolysis/gluconeogenesis and metabolism of various amino acids. By contrast, in the VWM pons white matter, we found a decrease in oxidative phosphorylation. Taken together, our data show that brain regions are affected in parallel in VWM, but to different degrees. We found region-specific involvement of different cell types and discovered that cellular respiratory metabolism is differently affected across white matter regions in VWM. These region-specific changes help explain regional vulnerability to pathology in VWM.
HostingRepository	PRIDE
AnnounceDate	2023-06-28
AnnouncementXML	Submission_2023-06-28_05:14:16.490.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JodieMan
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	2023-03-14 09:00:30	ID requested
⏵ 1	2023-06-28 05:14:16	announced
2	2023-11-14 06:56:27	announced	2023-11-14: Updated project metadata.
3	2024-10-22 05:51:12	announced	2024-10-22: Updated project metadata.

submitter keyword: Astrocytopathy, Leukodystrophy,Vanishing white matter, Regional vulnerability

MariannaBugiani
contact affiliation	Department of Pathology, Amsterdam University Medical Centres, Amsterdam Neuroscience, Amsterdam, The Netherlands
contact email	m.bugiani@amsterdamumc.nl
lab head
JodieMan
contact affiliation	Amsterdam UMC - Location VUMc
contact email	j.man@amsterdamumc.nl
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD040861
     1. Label: PRIDE project
     2. Name: Regional vulnerability of brain white matter in VWM