PXD047941 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | The link between Amyloid β and ferroptosis pathway in Alzheimer’s disease |
Description | Alzheimer’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. |
HostingRepository | PRIDE |
AnnounceDate | 2025-05-06 |
AnnouncementXML | Submission_2025-05-06_12:26:47.053.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Justina Clarinda Wolters |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-12-19 05:14:08 | ID requested | |
⏵ 1 | 2025-05-06 12:26:47 | announced | |
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 affiliation | Department of Pediatrics, University of Groningen, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands |
contact email | j.c.wolters@umcg.nl |
lab head | |
Justina Clarinda Wolters |
contact affiliation | UMCG |
contact email | j.c.wolters@umcg.nl |
dataset submitter | |
Full Dataset Link List
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/PXD047941 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD047941
- Label: PRIDE project
- Name: The link between Amyloid β and ferroptosis pathway in Alzheimer’s disease