PXD026529

PXD026529 is an original dataset announced via ProteomeXchange.

Title	Identification of early neurodegenerative pathways in progressive multiple sclerosis
Description	Progressive multiple sclerosis (MS) is characterized by unrelenting neurodegeneration, which causes cumulative disability and is refractory to current treatments. Drug development to prevent disease progression is an urgent clinical need yet is constrained by an incomplete understanding of its complex pathogenesis. Using spatial transcriptomics and proteomics on fresh-frozen human MS brain tissue, we identified multicellular mechanisms of progressive MS pathogenesis and traced their origin in relation to spatially distributed stages of neurodegeneration. By resolving ligand–receptor interactions in local microenvironments, we discovered defunct trophic and anti-inflammatory intercellular communications within areas of early neuronal decline. Proteins associated with neuronal damage in patient samples showed mechanistic concordance with published in vivo knockdown and central nervous system (CNS) disease models, supporting their causal role and value as potential therapeutic targets in progressive MS. Our findings provide a new framework for drug development strategies, rooted in an understanding of the complex cellular and signaling dynamics in human diseased tissue that facilitate this debilitating disease.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:37:31.525.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Fabian Coscia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-07 02:46:42	ID requested
1	2022-06-05 20:38:44	announced
⏵ 2	2024-10-22 05:37:31	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Multiple Sclerosis Spatial Proteomics

Lars Fugger
contact affiliation	University of Oxford
contact email	lars.fugger@ndcn.ox.ac.uk
lab head
Fabian Coscia
contact affiliation	Max Delbrueck Center for Molecular Medicine
contact email	fabian.coscia@cpr.ku.dk
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/2022/06/PXD026529

PRIDE project URI

• PRIDE
  1. PXD026529
     1. Label: PRIDE project
     2. Name: Identification of early neurodegenerative pathways in progressive multiple sclerosis