PXD063272

PXD063272 is an original dataset announced via ProteomeXchange.

Title	An approach to characterize mechanisms of action of anti-amyloidogenic compounds in vitro and in situ
Description	Amyloid 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.
HostingRepository	PRIDE
AnnounceDate	2025-05-26
AnnouncementXML	Submission_2025-05-25_20:29:16.232.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tetiana Serdiuk
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: 10116; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-04-24 00:41:44	ID requested
⏵ 1	2025-05-25 20:29:17	announced

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]

submitter keyword: alpha-synuclein, anti-amyloidogenic compounds,LiP-MS

Paola Picotti
contact affiliation	Institute of Molecular Systems Biology, ETH Zurich
contact email	picotti@imsb.biol.ethz.ch
lab head
Tetiana Serdiuk
contact affiliation	Institute of Molecular Systems Biology, ETH Zurich, Switzerland
contact email	tserdiuk@ethz.ch
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/2025/05/PXD063272

PRIDE project URI

• PRIDE
  1. PXD063272
     1. Label: PRIDE project
     2. Name: An approach to characterize mechanisms of action of anti-amyloidogenic compounds in vitro and in situ