Iron stored in ferritin is chemically reduced in the presence of aggregating Aβ(1-42)

Autor:	Peter J. Sadler, Jon Dobson, Jake Brooks, Peter B. O’Connor, Frederik Lermyte, Neil D. Telling, Joanna F. Collingwood, James Everett
Jazyk:	angličtina
Rok vydání:	2020
Předmět:	0301 basic medicine Microscopy Electron Scanning Transmission Iron lcsh:Medicine Peptide medicine.disease_cause Q1 Article Pathogenesis 03 medical and health sciences Protein Aggregates 0302 clinical medicine Alzheimer Disease medicine Humans Potential source lcsh:Science chemistry.chemical_classification Multidisciplinary Amyloid beta-Peptides biology Neurodegenerative diseases lcsh:R Spectrometry X-Ray Emission Alzheimer's disease R1 Peptide Fragments Ferritin Oxidative Stress 030104 developmental biology Biochemistry chemistry Metals Toxicity Ferritins biology.protein Ferric Biomarker (medicine) Dementia lcsh:Q Peptides Oxidation-Reduction 030217 neurology & neurosurgery Oxidative stress Biomarkers medicine.drug
Zdroj:	Scientific Reports, Vol 10, Iss 1, Pp 1-16 (2020) Scientific Reports
ISSN:	2045-2322
Popis:	Atypical low-oxidation-state iron phases in Alzheimer’s disease (AD) pathology are implicated in disease pathogenesis, as they may promote elevated redox activity and convey toxicity. However, the origin of low-oxidation-state iron and the pathways responsible for its formation and evolution remain unresolved. Here we investigate the interaction of the AD peptide β-amyloid (Aβ) with the iron storage protein ferritin, to establish whether interactions between these two species are a potential source of low-oxidation-state iron in AD. Using X-ray spectromicroscopy and electron microscopy we found that the co-aggregation of Aβ and ferritin resulted in the conversion of ferritin’s inert ferric core into more reactive low-oxidation-states. Such findings strongly implicate Aβ in the altered iron handling and increased oxidative stress observed in AD pathogenesis. These amyloid-associated iron phases have biomarker potential to assist with disease diagnosis and staging, and may act as targets for therapies designed to lower oxidative stress in AD tissue.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::016282e88fe429d0b0fa27410977104b http://link.springer.com/article/10.1038/s41598-020-67117-z Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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