Proteomics

Dataset Information

0

Mass spectrometry-based proteomics analysis of human globus pallidus from progressive supranuclear palsy patients discovers multiple disease pathways


ABSTRACT: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder clinically characterized by progressive postural instability, supranuclear gaze palsy, parkinsonism, and cognitive decline caused by degeneration in specific areas of the brain including globus pallidus (GP), substantia nigra, and subthalamic nucleus. However, the pathogenetic mechanism of PSP remains unclear to date. Unbiased global proteome analysis of patients’ brain samples is an important step toward understanding PSP pathogenesis, as proteins serve as workhorses and building blocks of the cell. In this study, we conducted unbiased mass spectrometry-based global proteome analysis of GP samples from 15 PSP patients, 15 Parkinson disease (PD) patients, and 15 healthy control (HC) individuals. To analyze 45 samples, we conducted 5 batches of 11-plex isobaric tandem mass tag (TMT)-based multiplexing experiments, identifying 10,231 proteins. The gene set enrichment analysis results showed that the PD pathway was the most highly enriched, followed by pathways for oxidative phosphorylation, Alzheimer disease, Huntington disease, and non-alcoholic fatty liver disease (NAFLD) when PSP was compared to HC or PD. Most of the proteins enriched in the gene set enrichment analysis were mitochondrial proteins such as cytochrome c oxidase, NADH dehydrogenase, acyl carrier protein, succinate dehydrogenase, ADP/ATP translocase, cytochrome b-c1 complex, and/or ATP synthase. Strikingly, all of the enriched mitochondrial proteins in the PD pathway were downregulated in PSP compared to both HC and PD. The subsequent Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) protein-protein interaction (PPI) analysis and the weighted gene co-expression network analysis (WGCNA) further supported that the mitochondrial proteins were the most highly enriched in PSP. This is the first global proteome analysis of human GP from PSP patients, and this study paves the way to understanding the pathogenesis mechanism of PSP.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

DISEASE(S): Progressive Supranuclear Palsy

SUBMITTER: chanhyun na  

LAB HEAD: Chan Hyun Na

PROVIDER: PXD031648 | Pride | 2022-12-08

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
PSP_GP_Set1_33p_.msf Msf
PSP_GP_Set1_33p__F01.raw Raw
PSP_GP_Set1_33p__F02.raw Raw
PSP_GP_Set1_33p__F03.raw Raw
PSP_GP_Set1_33p__F04.raw Raw
Items per page:
1 - 5 of 126
altmetric image

Publications

Mass spectrometry-based proteomics analysis of human globus pallidus from progressive supranuclear palsy patients discovers multiple disease pathways.

Jang Yura Y   Thuraisamy Thujitha T   Redding-Ochoa Javier J   Pletnikova Olga O   Troncoso Juan C JC   Rosenthal Liana S LS   Dawson Ted M TM   Pantelyat Alexander Y AY   Na Chan Hyun CH  

Clinical and translational medicine 20221101 11


<h4>Background</h4>Progressive supranuclear palsy (PSP) is a neurodegenerative disorder clinically characterized by progressive postural instability, supranuclear gaze palsy, parkinsonism, and cognitive decline caused by degeneration in specific areas of the brain including globus pallidus (GP), substantia nigra, and subthalamic nucleus. However, the pathogenetic mechanism of PSP remains unclear to date.Unbiased global proteome analysis of patients' brain samples is an important step toward unde  ...[more]

Similar Datasets

2022-12-08 | PXD037684 | Pride
2020-10-19 | PXD014371 | Pride
2010-06-24 | E-GEOD-17428 | biostudies-arrayexpress
2010-06-24 | E-GEOD-17445 | biostudies-arrayexpress
2011-01-29 | E-GEOD-26909 | biostudies-arrayexpress
2011-11-23 | E-GEOD-32037 | biostudies-arrayexpress
2011-11-23 | E-GEOD-32040 | biostudies-arrayexpress
2011-11-23 | E-GEOD-32039 | biostudies-arrayexpress
2022-08-02 | PXD031459 | Pride
2011-11-23 | GSE32039 | GEO