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PXD063272

PXD063272 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAn approach to characterize mechanisms of action of anti-amyloidogenic compounds in vitro and in situ
DescriptionAmyloid aggregation is associated with neurodegenerative disease and its modulation is a focus of drug development. We developed a pipeline based on limited proteolysis-mass spectrometry (LiP-MS) to probe the mechanism of action of anti-amyloidogenic compounds. Our approach identifies putative interaction sites, can probe compound interactions with specific target conformations in complex extracts, and identifies off-targets. We analysed interactions of six anti-amyloidogenic compounds and the amyloid binder Thioflavin T with different structural forms of the Parkinson’s disease protein α-Synuclein. AC Immune compound 2 interacted with α-Synuclein in vitro, in intact neurons and in neuronal lysates, reduced neuronal α-Synuclein levels in a seeded model, and had protective effects. EGCG, Baicalein, ThT and doxycycline interacted with α-Synuclein in vitro but not substantially in mammalian cell lysates, with many additional putative targets. Our modular pipeline will enable in situ screening of compounds against any amyloid aggregates and mechanistic studies of compound action.
HostingRepositoryPRIDE
AnnounceDate2025-05-26
AnnouncementXMLSubmission_2025-05-25_20:29:16.232.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterTetiana Serdiuk
SpeciesList scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-04-24 00:41:44ID requested
12025-05-25 20:29:17announced
Publication List
10.1038/s41531-025-00966-5;
Stalder P, Serdiuk T, Ghosh D, Fleischmann Y, Ait-Bouziad N, Quast JP, Malinovska L, Ouared A, Davranche A, Haenseler W, Boudou C, Tsika E, St, ö, hr J, Melki R, Riek R, de Souza N, Picotti P, An approach to characterize mechanisms of action of anti-amyloidogenic compounds in vitro and in situ. NPJ Parkinsons Dis, 11(1):122(2025) [pubmed]
Keyword List
submitter keyword: alpha-synuclein, anti-amyloidogenic compounds,LiP-MS
Contact List
Paola Picotti
contact affiliationInstitute of Molecular Systems Biology, ETH Zurich
contact emailpicotti@imsb.biol.ethz.ch
lab head
Tetiana Serdiuk
contact affiliationInstitute of Molecular Systems Biology, ETH Zurich, Switzerland
contact emailtserdiuk@ethz.ch
dataset submitter
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Dataset FTP location
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