PXD045531

PXD045531 is an original dataset announced via ProteomeXchange.

Title	Cathepsin B Promotes Aβ Proteotoxicity by Modulating Aging Regulating Mechanisms
Description	While the activities of certain proteases promote proteostasis and prevent neurodegeneration-associated phenotypes, the protease cathepsin B (CTSB) enhances proteotoxicity in Alzheimer’s disease (AD) model mice, and its levels are elevated in brains of AD patients. How CTSB exacerbates the toxicity of the AD-causing Amyloid β (Aβ), is controversial. Using an activity-based probe, aging-altering interventions and the nematode C. elegans we discovered that the CTSB CPR-6 promotes Aβ proteotoxicity but mitigates the toxicity of polyQ stretches. While the knockdown of cpr-6 does not affect lifespan, it alleviates Aβ toxicity by reducing the expression of swsn-3 and elevating the level of the protein SMK-1, both involved in the regulation of aging. These observations unveil a novel mechanism by which CTSB aggravates Aβ–mediated toxicity, indicate that it plays opposing roles in the face of distinct proteotoxic insults and highlight the importance of tailoring specific remedies for distinct neurodegenerative disorders.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:57:39.406.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Atif Ahmed
SpeciesList	scientific name: Caenorhabditis elegans; NCBI TaxID: 6239;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-20 11:35:59	ID requested
1	2024-09-03 08:45:55	announced
⏵ 2	2024-10-22 06:57:39	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Proteotoxicity, Aging,Cathepsin B, Neurodegeneration

Ehud Cohen
contact affiliation	Department of molecular Biology and Biochemistry, Institute of Medical Research Israel-Canada (IMRIC), Faculty of Medicine, Hebrew University of Jerusalem, Israel.
contact email	ehudc@ekmd.huji.ac.il
lab head
Atif Ahmed
contact affiliation	PhD student
contact email	siddiqatif@gmail.com
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/2024/09/PXD045531

PRIDE project URI

• PRIDE
  1. PXD045531
     1. Label: PRIDE project
     2. Name: Cathepsin B Promotes Aβ Proteotoxicity by Modulating Aging Regulating Mechanisms