PXD036301-1

PXD036301 is an original dataset announced via ProteomeXchange.

Title	Endogenous alpha-synuclein is essential for the transfer of pathology by exosomes, following PFF inoculation in vivo.
Description	Alpha-Synuclein (α-Syn) association with exosomes has been extensively studied both as a physiological process but also as a means of disease transmission under pathological conditions, via an elusive mechanism. Here, we utilized the preformed fibril (PFF) mouse model, as a source of brain-derived exosomes and assessed their pathogenic capacity following intrastriatal injections in host wild type (WT) mouse brain. We further investigated the impact of PFF toxic stimulus in the exosomal cargo independent of the endogenous α-Syn, by isolating exosomes from PFF-injected α-Syn knockout mice. We found that PFF inoculation does not alter the morphology, size distribution, and quantity of brain-derived exosomes, however we show, for the first time, that it triggers changes in the exosomal protein cargo related to synaptic and mitochondrial function, as well as metabolic processes. Importantly, we showed that the presence of the endogenous α-Syn is essential for the exosomes to acquire a pathogenic identity/status, allowing them to mediate disease transmission by inducing phospho-α-Syn pathology, astrogliosis and synaptic alterations in the host mouse brain, thus supporting a role of exosomes in a prion-like mode of infection.
HostingRepository	PRIDE
AnnounceDate	2023-08-04
AnnouncementXML	Submission_2023-08-04_00:30:02.030.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	MartinaSamiotaki
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-25 14:56:33	ID requested
⏵ 1	2023-08-04 00:30:02	announced
2	2024-10-22 05:59:45	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: pathology transmission, exosomes,Alpha-Synuclein (α-Syn), spreading, Parkinson’s disease, PFF

KaterinaMelachroinou
contact affiliation	Center of Basic Science, Biomedical Research Foundation of the Academy of Athens, Athens, Greece
contact email	kmelachr@bioacademy.gr
lab head
MartinaSamiotaki
contact affiliation	Protein Analysis Laboratory B.S.R.C. "Alexander Fleming", Alexander Fleming Street 34 16672, Vari, Greece
contact email	samiotaki@fleming.gr
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/2023/08/PXD036301

PRIDE project URI

• PRIDE
  1. PXD036301
     1. Label: PRIDE project
     2. Name: Endogenous alpha-synuclein is essential for the transfer of pathology by exosomes, following PFF inoculation in vivo.