PXD008099

PXD008099 is an original dataset announced via ProteomeXchange.

Title	Integrative Characterization of the R6/2 Mouse Brain Model of Huntington Disease Reveals Dysfunctional Neurotransmitter Metabolism
Description	Huntington disease (HD) is a fatal neurodegenerative disease, where dysfunction and loss of striatal and cortical neurons are central to the pathogenesis of the disease. Here, we integrated quantitative studies to investigate the underlying mechanisms behind HD pathology in a systems-wide manner. To this end, we used state-of-the-art mass spectrometry (MS) to establish a spatial brain proteome from late-stage R6/2 mice and compared this to wild-type (WT) counterparts. From the quantitative analysis, we observed altered expression of proteins in pathways related to energy metabolism, synapse function, and neurotransmitter homeostasis. To support these findings, metabolic 13C labelling studies confirmed a compromised astrocytic regulation of glutamate-GABA-glutamine cycling resulting in impaired release of glutamine and GABA synthesis. In recent years increasing attention has been focused on the role of astrocytes in HD, and our data supports that therapeutic strategies to improve astrocytic glutamine metabolism may help ameliorate symptoms in HD.
HostingRepository	PRIDE
AnnounceDate	2019-01-11
AnnouncementXML	Submission_2019-01-11_05:02:37.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Niels Henning Skotte
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	2017-11-01 02:27:27	ID requested
⏵ 1	2019-01-11 05:02:38	announced

Skotte NH, Andersen JV, Santos A, Aldana BI, Willert CW, N, ø, rrem, ø, lle A, Waagepetersen HS, Nielsen ML, Integrative Characterization of the R6/2 Mouse Model of Huntington's Disease Reveals Dysfunctional Astrocyte Metabolism. Cell Rep, 23(7):2211-2224(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: High resolution LC-MS, GS-MS, Proteome, Huntington disease, glutamine and glutamate metabolism, Glutamatergic and GABAergic neurons

Michael L. Nielsen
contact affiliation	Faculty of Health Sciences, Department of Proteomics, The Novo Nordisk Foundation Centre for Protein Research, University of Copenhagen, DK-2200 Copenhagen, Denmark
contact email	michael.lund.nielsen@cpr.ku.dk
lab head
Niels Henning Skotte
contact affiliation	University of Copenhagen
contact email	niels.skotte@cpr.ku.dk
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/2019/01/PXD008099

PRIDE project URI

• PRIDE
  1. PXD008099
     1. Label: PRIDE project
     2. Name: Integrative Characterization of the R6/2 Mouse Brain Model of Huntington Disease Reveals Dysfunctional Neurotransmitter Metabolism