PXD019279

PXD019279 is an original dataset announced via ProteomeXchange.

Title	Proteomic Profiling of the Substantia Nigra to Identify Determinants of Lewy Body Pathology and Dopaminergic Neuronal Loss
Description	Proteinaceous aggregates containing alpha-synuclein protein called Lewy bodies in the substantia nigra is a hallmark of Parkinson's disease. The molecular mechanisms of Lewy body formation and associated neuronal loss remain largely unknown. To gain insights on proteins and pathways associated with Lewy body pathology, we performed quantitative profiling of the proteome. We analyzed substantia nigra tissue from 51 subjects arranged into three groups: cases with Lewy body pathology, Lewy body-negative controls with matching neuronal loss and controls with no neuronal loss. Using label-free LC-MS/MS approach we quantified the 2,963 most abundant proteins. Statistical testing for differential protein abundance, followed by pathway enrichment and Bayesian learning of the causal network structure were performed to identify likely drivers of Lewy body formation and dopaminergic neuronal loss. The identified pathways include (1) Arp2/3 complex-mediated actin nucleation; (2) synaptic function; (3) poly(A) RNA binding; (4) basement membrane and endothelium; and (5) hydrogen peroxide metabolic process. According to the data, the endothelial/basement membrane pathway is tightly connected with both pathologies and likely to be one of the drivers of the neuronal loss. The poly(A) RNA-binding proteins, including the ones relevant to other neurodegenerative disorders (e.g. TDP-43 and FUS) have strong inverse correlation with Lewy bodies and may reflect alternative mechanism of nigral neurodegeneration.
HostingRepository	PRIDE
AnnounceDate	2022-08-11
AnnouncementXML	Submission_2022-08-11_09:41:23.073.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Matthew Monroe
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-18 17:40:36	ID requested
⏵ 1	2022-08-11 09:41:23	announced

Petyuk VA, Yu L, Olson HM, Yu F, Clair G, Qian WJ, Shulman JM, Bennett DA, Proteomic Profiling of the Substantia Nigra to Identify Determinants of Lewy Body Pathology and Dopaminergic Neuronal Loss. J Proteome Res, 20(5):2266-2282(2021) [pubmed]

submitter keyword: Brain, Lewy bodies, substantia nigra, LC-MS/MS

Vladislav A Petyuk
contact affiliation	Pacific Northwest National Laboratory
contact email	vladislav.petyuk@pnnl.gov
lab head
Matthew Monroe
contact affiliation	Pacific Northwest National Laboratory
contact email	matthew.monroe@pnnl.gov
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/2022/08/PXD019279

PRIDE project URI

• PRIDE
  1. PXD019279
     1. Label: PRIDE project
     2. Name: Proteomic Profiling of the Substantia Nigra to Identify Determinants of Lewy Body Pathology and Dopaminergic Neuronal Loss