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PXD034163

PXD034163 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleChlorpyrifos oxon crosslinking of amyloid beta 42 peptides is a new route for generation of self-aggregating amyloidogenic oligomers that promote Alzheimer’s disease
DescriptionEpidemiological evidence suggests that people chronically exposed to organophosphorus pesticides are at increased risk of neurodegenerative disease. Covalently linked amyloid beta dimers have been isolated from the brains of Alzheimer’s patients. The toxic forms of amyloid beta are amyloid dimers that spontaneously oligomerize. In the present report we treated recombinant and synthetic amyloid beta (1-42) with 1 mM chlorpyrifos oxon or 1 mM paraoxon. The trypsin-digested samples were analyzed by liquid chromatography tandem mass spectrometry on an Orbitrap Fusion Lumos mass spectrometer. Data were searched with Protein Prospector software. We found two new types of crosslinks in amyloid dimers. An isopeptide Asp-Asp link occurred between the N-terminal amine of Asp 1 in one peptide and the beta carboxyl group of Asp 1 in another peptide. An Asp-Arg link occurred between the guanidino group of Arg 5 in one peptide and the beta carboxyl group of Asp 1 in another peptide. These results show that the active metabolites of the pesticides chlorpyrifos and parathion catalyze the crosslinking of amyloid beta (1-42) into toxic dimers. It was concluded that the increased risk of neurodegenerative disease in people exposed to organophosphorus pesticides could be explained by the crosslinking activity of these chemicals.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:38:24.490.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterLawrence Schopfer
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-05-27 06:36:11ID requested
12022-07-17 09:01:09announced
22024-10-22 05:38:25announced2024-10-22: Updated project metadata.
Publication List
10.1016/j.cbi.2022.110029;
Onder S, Biberoglu K, Tacal O, Schopfer LM, Chlorpyrifos oxon crosslinking of amyloid beta 42 peptides is a new route for generation of self-aggregating amyloidogenic oligomers that promote Alzheimer's disease. Chem Biol Interact, 363():110029(2022) [pubmed]
Keyword List
submitter keyword: chlorpyrifos oxon, amyloid beta,isopeptide, crosslinks
Contact List
Oksana Lockridge
contact affiliationEppley Institute University of Nebraska Medical School USA
contact emailolockrid@unmc.edu
lab head
Lawrence Schopfer
contact affiliationUniversity of Nebraska Medical Center
contact emaillmschopf@unmc.edu
dataset submitter
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Dataset FTP location
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