PXD045561-1

PXD045561 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	2024-09-04
AnnouncementXML	Submission_2024-09-13_11:56:45.554.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yong-hong Yan
SpeciesList	scientific name: Caenorhabditis elegans; NCBI TaxID: 6239;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-21 06:40:59	ID requested
⏵ 1	2024-09-13 11:56:45	announced

Dataset with its publication pending

submitter keyword: Cathepsin B ,C. elegans,Aβ Proteotoxicity

Meng-Qiu Dong
contact affiliation	National Institute of Biological Sciences, Beijing
contact email	dongmengqiu@nibs.ac.cn
lab head
Yong-hong Yan
contact affiliation	National Institute of Biological Sciences, Beijing
contact email	yanyonghong@nibs.ac.cn
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/PXD045561

PRIDE project URI

• PRIDE
  1. PXD045561
     1. Label: PRIDE project
     2. Name: Cathepsin B Promotes Aβ Proteotoxicity by Modulating Aging Regulating Mechanisms