PXD023562-1

PXD023562 is an original dataset announced via ProteomeXchange.

Title	Broad Kinase Inhibition Mitigates Early Neuronal Dysfunction in Tauopathy
Description	Tauopathies are a group of more than twenty known disorders that involve progressive neurodegeneration, cognitive decline, and pathological tau accumulation. Current therapeutic strategies provide only limited, late-stage symptomatic treatment. This is partly due to lack of understanding of the molecular mechanisms linking tau and cellular dysfunction, especially during the early stages of disease progression. In this study, we treated tau transgenic mice with a multi-target kinase inhibitor to identify novel targets that contribute to cognitive impairment and exhibit therapeutic potential. Drug treatment significantly ameliorated brain atrophy and neuronal function as determined by behavioral testing and a sensitive imaging technique called manganese-enhanced magnetic resonance imaging (MEMRI) with quantitative R1 mapping. Surprisingly, these benefits occurred despite unchanged hyperphosphorylated tau levels. To elucidate the mechanism behind these improved cognitive outcomes, we performed quantitative proteomics to determine the altered protein network during this early stage in tauopathy and compare this model with the human AD proteome. We identified a cluster of preserved pathways shared with human tauopathy with striking potential for broad multi-target kinase intervention. We further report high confidence
HostingRepository	PRIDE
AnnounceDate	2021-02-02
AnnouncementXML	Submission_2021-02-01_23:43:30.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Duc Duong
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-13 00:15:41	ID requested
⏵ 1	2021-02-01 23:43:30	announced

Dataset with its publication pending

submitter keyword: Mouse LC-MS/MS

Jose F. Abisambra
contact affiliation	1Department of Neuroscience & Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL, USA
contact email	j.abisambra@ufl.edu
lab head
Duc Duong
contact affiliation	Center of Neurodegenerative Diseases
contact email	dduong@emory.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023562
     1. Label: PRIDE project
     2. Name: Broad Kinase Inhibition Mitigates Early Neuronal Dysfunction in Tauopathy