PXD013691-1

PXD013691 is an original dataset announced via ProteomeXchange.

Title	Molecular signatures of neuroinflammation induced by α-synuclein aggregates-A multi-proteomics approach (Mouse Arm)
Description	Alpha-synuclein aggregates (αSynAgg) are pathological hallmarks of Parkinson’s disease (PD) that induce microglial activation and immune-mediated neurotoxicity, although the molecular mechanisms of αSynAgg-induced immune activation are poorly defined. We used mass spectrometry to define proteomic changes induced by αSynAgg using in-vitro mouse microglia and an in-vivo fly (Drosophila melanogaster) model with neuron-specific αSyn overexpression. In mouse microglia, αSynAgg induced robust pro-inflammatory activation (increased expression of 864 genes including Irg1, Ifit1 and Pyhin) and increased nuclear proteins involved in RNA synthesis, splicing and anti-viral defense mechanisms. Conversely, αSynAgg decreased expression of 530 proteins (including Cdc123, Sod1 and Grn), which were predominantly cytosolic and involved in antigen presentation as well as metabolic, proteosomal and lysosomal mechanisms. Pathway analyses and confirmatory in -vitro studies suggested that αSynAgg partly mediates its effects via Stat3 activation. 26 proteins differentially-expressed by αSynAgg were also identified as PD risk genes in genome-wide association studies (upregulated: Brd2, Clk1, Siglec1; down-regulated: Memo1, Arhgap18, Fyn and PGgrn/Grn). We then validated progranulin (PGrn/Grn) as a lysosomal PD-associated protein that is decreased in striatal and nigral microglia in post-mortem PD brain compared to non-disease controls, congruent with our in -vitro findings.
HostingRepository	PRIDE
AnnounceDate	2020-01-24
AnnouncementXML	Submission_2020-01-24_00:23:53.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eric Dammer
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2019-05-02 01:34:11	ID requested
⏵ 1	2020-01-24 00:23:54	announced

Dataset with its publication pending

submitter keyword: mouse, microglia, alpha synuclein aggregates, SNCA, Parkinsons Disease

Srikant Rangaraju
contact affiliation	Department of Neurology, Emory University, Atlanta, GA 30322, US
contact email	srikant.rangaraju@emory.edu
lab head
Eric Dammer
contact affiliation	Emory University
contact email	edammer@emory.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD013691
     1. Label: PRIDE project
     2. Name: Molecular signatures of neuroinflammation induced by α-synuclein aggregates-A multi-proteomics approach (Mouse Arm)