PXD035310

PXD035310 is an original dataset announced via ProteomeXchange.

Title	The proteome of neuromelanin granules in dementia with Lewy bodies
Description	Neuromelanin granules (NMGs) are organelle-like structures present in the human substantia nigra pars compacta. Besides neuromelanin, NMGs contain proteins, lipids and metals. As NMG-containing dopaminergic neurons are preferentially lost in Parkinson’s disease and dementia with Lewy bodies (DLB), it is assumed that NMGs may play a role in neurodegenerative processes. Until now, this role is not completely understood and needs further investigation. We therefore set up a proteomic study to identify differences in the proteomic profile of NMGs from DLB patients (n=5) compared to healthy controls (CTRL, n=5). We used a laser microdissection and mass-spectrometry-based approach, in which we used targeted mass spectrometric experiments for validation. In NMG-surrounding (SNSurr.) tissue of DLB patients, we found evidence for ongoing oxidative damage and an impairment of protein degradation. As a potentially disease-related mechanism, we found α-synuclein and protein S100A9 to be enriched in NMGs of DLB cases, while the abundance of several ribosomal proteins was significantly decreased. As S100A9 is known to be able to enhance the formation of toxic α-synuclein fibrils, this finding points towards an involvement of NMGs in pathogenesis, however the exact role of NMGs as either neuroprotective or neurotoxic needs to be further investigated. Nevertheless, our study provides evidence for an impairment of protein degradation, ongoing oxidative damage and accumulation of potentially neurotoxic protein aggregates to be central mechanisms of neurodegeneration in DLB.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:24:49.834.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Maximilian Wulf
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-13 08:38:41	ID requested
1	2023-02-14 02:31:24	announced
⏵ 2	2023-11-14 08:24:50	announced	2023-11-14: Updated project metadata.

Wulf M, Barkovits K, Schork K, Eisenacher M, Riederer P, Gerlach M, Eggers B, Marcus K, The Proteome of Neuromelanin Granules in Dementia with Lewy Bodies. Cells, 11(22):(2022) [pubmed]

submitter keyword: proteomics, stress granules, substantia nigra pars compacta, dementia with Lewy bodies, neurodegeneration,Neuromelanin granules

Katrin Marcus
contact affiliation	Medizinisches Proteom-Center, Medical Faculty, Ruhr-University Bochum, Bochum, Germany
contact email	katrin.marcus@ruhr-uni-bochum.de
lab head
Maximilian Wulf
contact affiliation	Medizinisches Proteom-Center, Ruhr-University Bochum
contact email	Maximilian.Wulf@ruhr-uni-bochum.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/02/PXD035310

PRIDE project URI

• PRIDE
  1. PXD035310
     1. Label: PRIDE project
     2. Name: The proteome of neuromelanin granules in dementia with Lewy bodies