PXD037684

PXD037684 is an original dataset announced via ProteomeXchange.

Title	Mass spectrometry-based proteomics analysis of human substantia nigra from Parkinson's disease patients identifies multiple pathways potentially involved in the disease
Description	Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN) of the brain. Despite decades of studies, the precise pathogenic mechanism of PD is still elusive. An unbiased proteomic analysis of PD patients’ brains allows the identification of critical proteins and molecular pathways that lead to dopamine cell death and α-synuclein deposition and the resulting devastating clinical symptoms. In this study, we conducted an in-depth proteome analysis of human SN tissues from 15 PD patients and 15 healthy control (HC) individuals combining Orbitrap mass spectrometry with the isobaric tandem mass tag (TMT)-based multiplexing technology. We identified 10,040 proteins with 1,140 differentially expressed proteins in the SN of PD patients. Pathway analysis showed that the ribosome pathway was the most enriched one, followed by GABAergic synapse, retrograde endocannabinoid signaling, cell adhesion molecules (CAMs), morphine addiction, Prion disease, and Parkinson's disease pathways. Strikingly, the majority of the proteins enriched in the ribosome pathway were mitochondrial ribosomal proteins (mitoribosomes; MRPs). The subsequent protein-protein interaction (PPI) analysis and the weighted gene co-expression network analysis (WGCNA) confirmed that the mitoribosome is the most enriched protein cluster. Furthermore, the mitoribosome was also identified in our analysis of a replication set of 10 PD and 9 HC SN tissues. This study provides potential disease pathways involved in PD and paves the way to study further the pathogenic mechanism of PD.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:33:23.370.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	chanhyun na
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-24 03:49:51	ID requested
1	2022-12-08 11:11:49	announced
⏵ 2	2023-11-14 08:33:24	announced	2023-11-14: Updated project metadata.

submitter keyword: proteomics,Parkinson's disease, mass spectrometry, mitoribosomes, human brain tissue, substantia nigra

Chan Hyun Na
contact affiliation	Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Department of Neurology, Johns Hopkins University
contact email	chanhyun@jhmi.edu
lab head
chanhyun na
contact affiliation	Johns Hopkins University
contact email	chanhyun.na@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD037684
     1. Label: PRIDE project
     2. Name: Mass spectrometry-based proteomics analysis of human substantia nigra from Parkinson's disease patients identifies multiple pathways potentially involved in the disease