PXD020499

PXD020499 is an original dataset announced via ProteomeXchange.

Title	CSF extracellular vesicle proteomics demonstrates altered protein homeostasis in amyotrophic lateral sclerosis
Description	Extracellular vesicles (EVs) are released by neurons and glia reach the cerebrospinal fluid (CSF). Studying the proteome of CSF-derived EVs offers a novel perspective on the key intracellular processes associated with the pathogenesis of the neurodegenerative disease amyotrophic lateral sclerosis (ALS) and a potential source from which to develop biomarkers. CSF EVs were extracted using ultrafiltration liquid chromatography from ALS patients and controls. EV size distribution and concentration was measured using nanoparticle tracking analysis and liquid chromatography-tandem mass spectrometry proteomic analysis performed. CSF EV concentration and size distribution did not differ between ALS and control groups, nor between a sub-group of ALS patients with or without an associated hexanucleotide repeat expansion (HRE) in C9orf72. Univariate proteomic analysis identified downregulation of the pentameric proteasome-like protein Bleomycin hydrolase in ALS patients, whilst Gene Ontology enrichment analysis demonstrated downregulation of proteasome core complex proteins (8/8 proteins, normalized enrichment ratio -1.77, FDR-adjusted p = 0.057) in the ALS group. The sub-group of ALS patients associated with the C9orf72 HRE showed upregulation in Ubiquitin-like modifying-activating protein 1 (UBA1) compared to non-C9orf72 cases. Proteomic analysis of CSF EVs in ALS detects intracellular alterations in protein homeostatic mechanisms, previously only identified in pathological tissues. This supports the wider use of CSF EVs as a source of novel biomarkers reflecting key and potentially druggable pathological intracellular pathway alterations in ALS.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:28:27.209.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD020499
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Roman Fischer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-07-22 04:04:34	ID requested
1	2021-09-09 01:49:14	announced
⏵ 2	2024-10-22 05:28:35	announced	2024-10-22: Updated project metadata.

10.1186/s12014-020-09294-7;

10.6019/PXD020499;

Thompson AG, Gray E, M, ä, ger I, Th, é, z, é, nas ML, Charles PD, Talbot K, Fischer R, Kessler BM, Wood M, Turner MR, CSF extracellular vesicle proteomics demonstrates altered protein homeostasis in amyotrophic lateral sclerosis. Clin Proteomics, 17():31(2020) [pubmed]

submitter keyword: CSF, ALS

Roman Fischer
contact affiliation	Target Discovery Institute
contact email	roman.fischer@ndm.ox.ac.uk
lab head
Roman Fischer
contact affiliation	University of Oxford
contact email	roman.fischer@ndm.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD020499
     1. Label: PRIDE project
     2. Name: CSF extracellular vesicle proteomics demonstrates altered protein homeostasis in amyotrophic lateral sclerosis