PXD009717

PXD009717 is an original dataset announced via ProteomeXchange.

Title	Induction of the immunoproteasome subunit Lmp7 links proteostasis and immunity in α-synuclein aggregation disorders, part 1
Description	Accumulation of aggregated α-synuclein into Lewy bodies is thought to contribute to the onset and progression of dopaminergic neuron degeneration in Parkinson’s disease (PD) and related disorders. Although protein aggregation is associated with perturbation of proteostasis, how α-synuclein aggregation affects the brain proteome and signaling remains uncertain. In a mouse model of α-synuclein aggregation, 6% of 6,215 proteins and 1.6% of 8,183 phosphopeptides changed in abundance, indicating conservation of proteostasis and phosphorylation signaling. The proteomic analysis confirmed changes in abundance of proteins that regulate dopamine synthesis and transport, synaptic activity and integrity, and unearthed changes in mRNA binding, processing and protein translation. Phosphorylation signaling changes centered on axonal and synaptic cytoskeletal organization and structural integrity. Proteostatic responses included a significant increase in the levels of Lmp7, a component of the immunoproteasome. Increased Lmp7 levels and activity were also quantified in postmortem human brains with PD and dementia with Lewy bodies. Functionally, the immunoproteasome degrades α-synuclein aggregates and generates potentially antigenic peptides. Expression and activity of the immunoproteasome may represent testable targets to induce adaptive responses that maintain proteome integrity and modulate immune responses in protein aggregation disorders.
HostingRepository	PRIDE
AnnounceDate	2018-05-18
AnnouncementXML	Submission_2018-05-18_00:11:12.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hossein Fazelinia
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2018-05-08 09:00:14	ID requested
⏵ 1	2018-05-18 00:11:13	announced

Ugras S, Daniels MJ, Fazelinia H, Gould NS, Yocum AK, Luk KC, Luna E, Ding H, McKennan C, Seeholzer S, Martinez D, Evans P, Brown D, Duda JE, Ischiropoulos H, -Synuclein Aggregation Disorders. EBioMedicine, 31():307-319(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: α-synuclein, immunoproteasome, proteomoe, phosphoproteome

Harry Ischiropoulos
contact affiliation	Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA
contact email	ischirop@pennmedicine.upenn.edu
lab head
Hossein Fazelinia
contact affiliation	Children's Hospital of Philadelphia
contact email	fazeliniah@email.chop.edu
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/2018/05/PXD009717

PRIDE project URI

• PRIDE
  1. PXD009717
     1. Label: PRIDE project
     2. Name: Induction of the immunoproteasome subunit Lmp7 links proteostasis and immunity in α-synuclein aggregation disorders, part 1