Proteomics

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Large-scale proteomics analysis of five brain regions from Parkinson’s disease patients with a GBA1 mutation


ABSTRACT: Despite being the second most common neurodegenerative disorder, little is known about Parkinson’s disease (PD) pathogenesis. A number of genetic factors predispose towards PD, among them mutations in GBA1, which encodes the lysosomal enzyme acid-β-glucosidase. We now perform non-targeted, mass spectrometry based quantitative proteomics on five brain regions from PD patients with a GBA1 mutation (PD-GBA) and compare to age- and sex-matched idiopathic PD patients and controls. Only two proteins were differentially-expressed in all five brain regions whereas significant differences were detected between the brain regions, with changes consistent with loss of dopaminergic neurons in the substantia nigra and activation of a number of pathways in the cingulate gyrus, including ceramide synthesis. Mitochondrial oxidative phosphorylation was inactivated to a larger extent in IPD samples compared to controls and to an even larger extent in PD-GBA. This is the first large-scale proteomics dataset generated for the study of PD-GBA.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

SUBMITTER: Meital Kupervaser  

LAB HEAD: Anthony H. Futerman

PROVIDER: PXD047134 | Pride | 2024-02-19

REPOSITORIES: Pride

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Large-scale proteomics analysis of five brain regions from Parkinson's disease patients with a GBA1 mutation.

Blumenreich Shani S   Nehushtan Tamar T   Kupervaser Meital M   Shalit Tali T   Gabashvili Alexandra A   Joseph Tammar T   Milenkovic Ivan I   Hardy John J   Futerman Anthony H AH  

NPJ Parkinson's disease 20240208 1


Despite being the second most common neurodegenerative disorder, little is known about Parkinson's disease (PD) pathogenesis. A number of genetic factors predispose towards PD, among them mutations in GBA1, which encodes the lysosomal enzyme acid-β-glucosidase. We now perform non-targeted, mass spectrometry based quantitative proteomics on five brain regions from PD patients with a GBA1 mutation (PD-GBA) and compare to age- and sex-matched idiopathic PD patients (IPD) and controls. Two proteins  ...[more]

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