PXD048913

PXD048913 is an original dataset announced via ProteomeXchange.

Title	Rat PC12 wild-type cells with polypharmacological drug PHOX15 treatment that reduces tau phosphorylation at disease-relevant sites and restores its physiological microtubule interaction
Description	In tauopathies such as Alzheimer's disease, the aggregation and increased phosphorylation of tau proteins are key pathological features. These changes in tau are strongly linked to neurodegeneration, making it a prime target for therapeutic intervention. Through chemoinformatic analyses, 2-phenyloxazole (PHOX) derivatives were identified as promising polypharmacological agents that could inhibit tau aggregation and modulate its phosphorylation. PHOX15 has been shown to restore the normal interaction of tau with microtubules in neurons and inhibit the initial phase of tau aggregation in vitro. Additionally, PHOX15 has been observed to suppress the activity of significant tau kinases, namely GSK3β and Cdk5, and decrease tau phosphorylation at sites relevant to disease progression. Molecular dynamics simulations have revealed that PHOX15's binding in tau protofilaments may hinder their transformation into PHF-like conformations. Complementary mass spectrometry experiments in Rat PC12 wild-type cells treated with PHOX15 demonstrated notable alterations in the kinome upon this treatment. This project highlights the potential of PHOX15 as a valuable drug candidate to mitigate tau-induced neurodegeneration. For more details, see Pinzi L, Conze C et al. “Quantitative Live Cell Imaging of a Tauopathy Model Enables the Identification of a Polypharmacological Drug Candidate That Restores Physiological Microtubule Regulation.” BioRxiv, 2022. https://doi.org/10.1101/2022.10.31.514565.
HostingRepository	PRIDE
AnnounceDate	2024-02-26
AnnouncementXML	Submission_2024-02-26_12:45:00.059.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD048913
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Nataliya Trushina
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-26 00:11:19	ID requested
⏵ 1	2024-02-26 12:45:00	announced

10.6019/PXD048913;

submitter keyword: tauopathy,Rat, kinase inhibitor, hyperphosphorylation, tau, LFQ, tau phosphorylation, phosphorylation, label-free, PC12

Roland Brandt
contact affiliation	Department of Neurobiology, School of Biology/Chemistry, Osnabrück University, Germany. Center for Cellular Nanoanalytics, Osnabrück University, Germany. Institute of Cognitive Science, Osnabrück University, Germany.
contact email	robrandt@uni-osnabrueck.de
lab head
Nataliya Trushina
contact affiliation	Osnabrück University
contact email	natrushina@uni-osnabrueck.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD048913
     1. Label: PRIDE project
     2. Name: Rat PC12 wild-type cells with polypharmacological drug PHOX15 treatment that reduces tau phosphorylation at disease-relevant sites and restores its physiological microtubule interaction