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PXD010828

PXD010828 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleNeurodegenerative disease mouse model SDS-insoluble proteins
DescriptionThe 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.
HostingRepositoryPRIDE
AnnounceDate2018-12-04
AnnouncementXMLSubmission_2018-12-04_03:59:02.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterGuilian Xu
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-08-20 06:29:24ID requested
12018-08-29 03:29:06announced
22018-12-04 03:59:04announcedUpdated project metadata.
Publication List
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]
Keyword List
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
Contact List
Guilian Xu
contact affiliationDepartment of Neuroscience, School of Medicine, University of Florida
contact emailxugl@ufl.edu
lab head
Guilian Xu
contact affiliationNeuroscience
contact emailxugl@ufl.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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