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PXD045565

PXD045565 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCathepsin B Promotes Aβ Proteotoxicity by Modulating Aging Regulating Mechanisms
DescriptionWhile 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.
HostingRepositoryPRIDE
AnnounceDate2024-09-03
AnnouncementXMLSubmission_2024-09-03_08:42:19.129.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAtif Ahmed
SpeciesList scientific name: Caenorhabditis elegans; NCBI TaxID: 6239;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-09-21 09:04:10ID requested
12024-09-03 08:42:19announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Cathepsin activity, Neurodegeneration, C.elegans
Contact List
Ehud Cohen
contact affiliationDepartment of Molecular Biology and Biochemistry, Institute for Medical Research Israel-Canada (IMRIC), Faculty of Medicine, Hebrew University of Jerusalem, Israel
contact emailehudc@ekmd.huji.ac.il
lab head
Atif Ahmed
contact affiliationPhD student
contact emailsiddiqatif@gmail.com
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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