PXD062289

PXD062289 is an original dataset announced via ProteomeXchange.

Title	proteomic analysis comparing HEK293tau cells and HEK293vec cells
Description	The accumulation of abnormal tau and insufficient degradation of lysosomes are both reported as pathological features within neurons of Alzheimer’s disease (AD) brain. Promoting lysosomal degradation of abnormal tau is expected to improve AD neurodegeneration. The assembly of vacuolar-type proton-pumping ATPase (V-ATPase) on lysosome membrane is crucial for maintaining the acidity and activities of the hydrolases in lysosomes. Here, the abnormal binding of phosphorylated tau to a V-ATPase subunit ATP6V1B2 was detected in tau burdened cells, with an elevated lysosome pH value and insufficient activation of hydrolases. Therefore a fragment of ATP6V1B2 was used to block the binding of tau to ATP6V1B2. After overexpression of this fragment we observed significant improvements in lysosome deacidification and hydrolases activation insufficiency in tau burdened cells, and the decreased hippocampal tau level and improved cognitive impairment in P301S mice. Furthermore, we identified a more effective fragment of ATP6V1B2, 120-157 a.a., that had a better ability to reduce the abnormal binding of tau to ATP6V1B2 in vitro. Injection of fragment 120-157 a.a. via tail vein reversed the brain tau burden and cognitive deficit in 3×Tg AD mice. All these data suggested that blocking the abnormal binding of tau to ATP6V1B2 helps restore the acidity of lysosomes and promote the degradation of abnormal tau. These findings also emphasize the protective role of improving lysosomal acidification strategies in the pathogenesis of AD and enhance their potentiality in clinical settings.
HostingRepository	iProX
AnnounceDate	2025-03-27
AnnouncementXML	Submission_2025-12-31_00:14:08.627.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yechao Yuan
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-26 21:09:26	ID requested
⏵ 1	2025-12-31 00:14:09	announced

Dataset with its publication pending

submitter keyword: human, kidney, tau

Qing Tian
contact affiliation	Huazhong University of Science and Technology
contact email	tianq@hust.edu.cn
lab head
Yechao Yuan
contact affiliation	Huazhong University of Science and Technology
contact email	ycy0528@hust.edu.cn
dataset submitter

iProX dataset URI