Proteomics

Dataset Information

0

Regional vulnerability of brain white matter in VWM


ABSTRACT: 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.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

DISEASE(S): Leukoencephalopathy With Vanishing White Matter

SUBMITTER: Jodie Man  

LAB HEAD: Marianna Bugiani

PROVIDER: PXD040861 | Pride | 2023-06-28

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20190804_Sprot_human.fasta Fasta
MQ-output.zip Other
Man00014_SA_Exp5_FR_WM_CTRL_1_1p5ug.raw Raw
Man00014_SA_Exp5_FR_WM_CTRL_2_1p5ug.raw Raw
Man00014_SA_Exp5_FR_WM_CTRL_4_1p5ug.raw Raw
Items per page:
1 - 5 of 18

Similar Datasets

2023-01-02 | PXD030831 | Pride
2015-03-12 | E-MTAB-3395 | biostudies-arrayexpress
2023-01-19 | ST002452 | MetabolomicsWorkbench
2017-07-11 | PXD005854 | Pride
2024-08-29 | PXD047800 | Pride
2019-03-13 | GSE111972 | GEO
2024-06-16 | PXD045041 | Pride
2021-09-10 | PXD023933 | Pride
2024-06-16 | PXD043872 | Pride
2012-08-01 | GSE35864 | GEO