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PXD047941

PXD047941 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe link between Amyloid β and ferroptosis pathway in Alzheimer’s disease
DescriptionAlzheimer’s disease (AD), currently affecting millions of people worldwide, is the most prevalent form of dementia. Treatment strategies aiming to interfere with the formation of amyloid β (Aβ) plaques and neurofibrillary tangles (NFTs), the two major AD hallmarks, have shown modest or no effect. Recent evidence suggests that ferroptosis, a type of programmed cell death caused by iron accumulation and lipid peroxidation, contributes to AD pathogenesis. Here we evaluate if Aβ is associated with ferroptosis pathways and whether ferroptosis inhibition could attenuate Aβ-related effects. The existing link between ferroptosis and AD has been largely based on cell culture and animal studies, while evidence from human brain tissue is limited. Performing positive pixel density scoring on immunohistochemically stained post mortem BA17 sections revealed that the progression of AD pathology was accompanied by decreased expression of nuclear receptor co-activator 4 (NCOA4) and glutathione peroxidase 4 (GPX4) in the grey matter (GM). The expression of ferroportin, NCOA4, GPX4, 4-hydroxy-2-nonenal (4HNE) and cytochrome C was significantly lower, while the expression of ferritin was higher in the Aβ plaque area compared to the immediate vicinity of the non-Aβ tissue in AD brain tissue. Taken together, these findings indicate a relationship between Aβ-related processes and the expression of ferroptosis-related proteins. Additionally, ferroptosis inhibition prevented Aβ pathology, decreased lipid peroxidation and restored iron storage in human AD iPSCs-derived brain cortical organoids (cBOs). Differential expression analysis of AD organoids compared to isogenic controls indicate activation of the ferroptotic pathway. This further supports the previously suggested link between Aβ-related pathology and ferroptosis. Determining the causality between development of Aβ plaques and deregulation of molecular pathways involved in ferroptosis is crucial for developing potential therapeutic interventions.
HostingRepositoryPRIDE
AnnounceDate2025-05-06
AnnouncementXMLSubmission_2025-05-06_12:26:47.053.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJustina Clarinda Wolters
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-12-19 05:14:08ID requested
12025-05-06 12:26:47announced
Publication List
10.1038/s41419-024-07152-0;
Majern, í, kov, á N, Marmolejo-Garza A, Salinas CS, Luu MDA, Zhang Y, Trombetta-Lima M, Tomin T, Birner-Gruenberger R, Lehtonen Š, Koistinaho J, Wolters JC, Ayton S, den Dunnen WFA, Dolga AM, and ferroptosis pathway in Alzheimer's disease progression. Cell Death Dis, 15(10):782(2024) [pubmed]
Keyword List
submitter keyword: lipid peroxidation,Neurodegeneration, iron dysregulation, amyloid β, brain organoid
Contact List
Justina Clarinda
contact affiliationDepartment of Pediatrics, University of Groningen, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands
contact emailj.c.wolters@umcg.nl
lab head
Justina Clarinda Wolters
contact affiliationUMCG
contact emailj.c.wolters@umcg.nl
dataset submitter
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