PXD010828 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
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 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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD010828
- Label: PRIDE project
- Name: Neurodegenerative disease mouse model SDS-insoluble proteins