PXD034163

PXD034163 is an original dataset announced via ProteomeXchange.

Title	Chlorpyrifos oxon crosslinking of amyloid beta 42 peptides is a new route for generation of self-aggregating amyloidogenic oligomers that promote Alzheimer’s disease
Description	Epidemiological 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:38:24.490.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lawrence Schopfer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-27 06:36:11	ID requested
1	2022-07-17 09:01:09	announced
⏵ 2	2024-10-22 05:38:25	announced	2024-10-22: Updated project metadata.

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]

submitter keyword: chlorpyrifos oxon, amyloid beta,isopeptide, crosslinks

Oksana Lockridge
contact affiliation	Eppley Institute University of Nebraska Medical School USA
contact email	olockrid@unmc.edu
lab head
Lawrence Schopfer
contact affiliation	University of Nebraska Medical Center
contact email	lmschopf@unmc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034163
     1. Label: PRIDE project
     2. Name: Chlorpyrifos oxon crosslinking of amyloid beta 42 peptides is a new route for generation of self-aggregating amyloidogenic oligomers that promote Alzheimer’s disease