PXD021396

PXD021396 is an original dataset announced via ProteomeXchange.

Title	CNS-derived extracellular vesicles from superoxide dismutase 1 (SOD1)G93A ALS mice originate from astrocytes and neurons and carry misfolded SOD1
Description	Extracellular vesicles (EVs) are secreted by myriad cells in culture and also by unicellular organisms, and their identification in mammalian fluids suggests that EV release also occurs at the organism level. However, although it is clearly important to better understand EVs' roles in organismal biology, EVs in solid tissues have received little attention. Here, we modified a protocol for EV isolation from primary neural cell culture to collect EVs from frozen whole murine and human neural tissues by serial centrifugation and purification on a sucrose gradient. Quantitative proteomics comparing brain-derived EVs from nontransgenic (NTg) and a transgenic amyotrophic lateral sclerosis (ALS) mouse model, superoxide dismutase 1 (SOD1) G93A , revealed that these EVs contain canonical exosomal markers and are enriched in synaptic and RNA-binding proteins. The compiled brain EV proteome contained numerous proteins implicated in ALS, and EVs from SOD1 G93A mice were significantly depleted in myelin-oligodendrocyte glycoprotein compared with those from NTg animals. We observed that brain- and spinal cord–derived EVs, from NTg and SOD1 G93A mice, are positive for the astrocyte marker GLAST and the synaptic marker SNAP25, whereas CD11b, a microglial marker, was largely absent. EVs from brains and spinal cords of the SOD1 G93A ALS mouse model, as well as from human SOD1 familial ALS patient spinal cord, contained abundant misfolded and nonnative disulfide-cross-linked aggregated SOD1. Our results indicate that CNS-derived EVs from an ALS animal model contain pathogenic disease-causing proteins and suggest that brain astrocytes and neurons, but not microglia, are the main EV source.
HostingRepository	PRIDE
AnnounceDate	2020-09-11
AnnouncementXML	Submission_2020-09-10_22:42:18.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jenny Moon
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Bruker Daltonics instrument model

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-10 01:38:26	ID requested
⏵ 1	2020-09-10 22:42:18	announced

Silverman JM, Christy D, Shyu CC, Moon KM, Fernando S, Gidden Z, Cowan CM, Ban Y, Stacey RG, Grad LI, McAlary L, Mackenzie IR, Foster LJ, Cashman NR, ALS mice originate from astrocytes and neurons and carry misfolded SOD1. J Biol Chem, 294(10):3744-3759(2019) [pubmed]

submitter keyword: exosome (vesicle), amyotrophic lateral sclerosis (ALS) (Lou Gehrig disease), neurodegeneration, proteomics, astrocyte, extracellular vesicles, central nervous system (CNS), secretion, protein homeostasis, mouse model

Neil R. Cashman
contact affiliation	Centre for Brain Health, Dept. of Medicine, University of British Columbia, Vancouver, British Columbia V6T 1B5, Canada
contact email	neil.cashman@vch.ca
lab head
Jenny Moon
contact affiliation	University of British Columbia
contact email	kyungmee@mail.ubc.ca
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/2020/09/PXD021396

PRIDE project URI

• PRIDE
  1. PXD021396
     1. Label: PRIDE project
     2. Name: CNS-derived extracellular vesicles from superoxide dismutase 1 (SOD1)G93A ALS mice originate from astrocytes and neurons and carry misfolded SOD1