PXD016015

PXD016015 is an original dataset announced via ProteomeXchange.

Title	Hsp110 Mitigates α-Synuclein Pathology In Vivo
Description	Parkinson’s disease is characterized by the aggregation of the presynaptic protein α-synuclein and its deposition into pathologic Lewy bodies. While extensive research has been carried out on mediators of α-synuclein aggregation, molecular facilitators of α-synuclein disaggregation are still generally unknown. We investigated the role of molecular chaperones in both preventing and disaggregating α-synuclein oligomers and fibrils, with a focus on the mammalian disaggregase complex. Here, we show that overexpression of the chaperone Hsp110 is sufficient to reduce α-synuclein aggregation in a mammalian cell culture model. Additionally, we demonstrate that Hsp110 effectively mitigates α-synuclein pathology in vivo through the characterization of transgenic Hsp110 and double transgenic α-synuclein/Hsp110 mouse models. Unbiased analysis of the synaptic proteome of these mice revealed that overexpression of Hsp110 can override the protein changes driven by the α-synuclein transgene. Furthermore, overexpression of Hsp110 is sufficient to prevent endogenous α-synuclein templating and spread following injection of aggregated α-synuclein seeds into brain, supporting a role for Hsp110 in the prevention and/or disaggregation of α-synuclein pathology.
HostingRepository	PRIDE
AnnounceDate	2020-05-26
AnnouncementXML	Submission_2020-05-26_14:52:59.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	TuKiet Lam
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; acetylated residue; iodoacetamide derivatized residue; hydrolyzed N-ethylmaleimide adduct; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-10-25 02:34:35	ID requested
⏵ 1	2020-05-26 14:53:00	announced

Taguchi YV, Gorenberg EL, Nagy M, Thrasher D, Fenton WA, Volpicelli-Daley L, Horwich AL, Chandra SS, -synuclein pathology in vivo. Proc Natl Acad Sci U S A, 116(48):24310-24316(2019) [pubmed]

submitter keyword: synapse, chaperone, Parkinson’s disease, alpha synuclein, disaggregate

Sreeganga Chandra
contact affiliation	Associate Professor of Neurology and Neuroscience
contact email	sreeganga.chandra@yale.edu
lab head
TuKiet Lam
contact affiliation	Yale University
contact email	tukiet.lam@yale.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/2020/05/PXD016015

PRIDE project URI

• PRIDE
  1. PXD016015
     1. Label: PRIDE project
     2. Name: Hsp110 Mitigates α-Synuclein Pathology In Vivo