PXD010828

PXD010828 is an original dataset announced via ProteomeXchange.

Title	Neurodegenerative disease mouse model SDS-insoluble proteins
Description	The deposition of pathologic misfolded proteins in neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia and amyotrophic lateral sclerosis is hypothesized to burden protein homeostatic (proteostatic) machinery, potentially leading to insufficient capacity to maintain the proteome. This hypothesis has been supported by previous work in our laboratory, as evidenced by the perturbation of cytosolic protein solubility in response to amyloid plaques in a mouse model of Alzheimer’s amyloidosis. In the current study, we demonstrate changes in proteome solubility are a common pathology to mouse models of neurodegenerative disease. Pathological accumulations of misfolded tau, α-synuclein and mutant superoxide dismutase 1 in CNS tissues of transgenic mice was associated with changes in the solubility of hundreds of CNS proteins in each model. We observed that changes in proteome solubility were progressive and, using the rTg4510 model of inducible tau pathology, demonstrated that these changes were dependent upon sustained expression of the primary pathologic protein. In all of the models examined, changes in proteome solubility were robust, easily detected, and provided a sensitive indicator of proteostatic disruption. Interestingly, a subset of the proteins that display a shift towards insolubility were common between these different models, suggesting that a specific subset of the proteome is vulnerable to proteostatic disruption. Overall, our data suggest that neurodegenerative proteinopathies modeled in mice impose a burden on the proteostatic network that diminishes the ability of neural cells to prevent aberrant conformational changes that alter the solubility of hundreds of abundant cellular proteins.
HostingRepository	PRIDE
AnnounceDate	2018-12-04
AnnouncementXML	Submission_2018-12-04_03:59:02.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Guilian Xu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-08-20 06:29:24	ID requested
1	2018-08-29 03:29:06	announced
⏵ 2	2018-12-04 03:59:04	announced	Updated project metadata.

Pace MC, Xu G, Fromholt S, Howard J, Crosby K, Giasson BI, Lewis J, Borchelt DR, Changes in proteome solubility indicate widespread proteostatic disruption in mouse models of neurodegenerative disease. Acta Neuropathol, 136(6):919-938(2018) [pubmed]

ProteomeXchange project tag: Human Brain Proteome Project (HUPO_HBPP) (B/D-HPP)

curator keyword: Biological

submitter keyword: Protein Misfolding, Proteomics, transgenic mice, LC-MS/MS

Guilian Xu
contact affiliation	Department of Neuroscience, School of Medicine, University of Florida
contact email	xugl@ufl.edu
lab head
Guilian Xu
contact affiliation	Neuroscience
contact email	xugl@ufl.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/2018/08/PXD010828

PRIDE project URI

• PRIDE
  1. PXD010828
     1. Label: PRIDE project
     2. Name: Neurodegenerative disease mouse model SDS-insoluble proteins