Fe(II) formation after interaction of the amyloid β-peptide with iron-storage protein ferritin
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The interaction of amyloid β-peptide (Aβ) with the iron-storage protein ferritin was studied in vitro. We have shown that Aβ during fibril formation process is able to reduce Fe(III) from the ferritin core (ferrihydrite) to Fe(II). The Aβ-mediated Fe(III) reduction yielded a two-times-higher concentration of free Fe(II) than the spontaneous formation of Fe(II) by the ferritin itself. We suggest that Aβ can also act as a ferritin-specific metallochaperone-like molecule capturing Fe(III) from the ferritin ferrihydrite core. Our observation may partially explain the formation of Fe(II)-containing minerals in human brains suffering by neurodegenerative diseases.
KeywordsFerritin Aβ Iron reduction Alzheimer’s disease Magnetite Metallochaperone
This work was supported by VEGA Grant Agency (project No. 2/0062/16, 2/0016/17, 0045, 2/0062/14, 2/0009/17), the Slovak Research and Development Agency (contract No. APVV-015-0453) and the Ministry of Education Agency for European Structural Funds (projects No. 26220120021, 2622012033, 26220220061, and 26220220186).
- 7.Everett, J., Cespedes, E., Shelford, L.R., Exley, C., Collingwood, J.F., Dobson, J., van der Laan, G., Jenkins, C.A., Arenholz, E., Telling, N.D.: Evidence of redox-active iron formation following aggregation of ferrihydrite and the Alzheimer’s disease peptide β-amyloid. Inorg. Chem. 53, 2803–2809 (2014)Google Scholar
- 13.Everett, J., Cespedes, E., Shelford, L.R., Exley, C., Collingwood, J.F., Dobson, J., van der Laan, G., Jenkins, C.A., Arenholz, E., Telling, N.D.: Ferrous iron formation following the co-aggregation of ferric iron and the Alzheimer’s disease peptide β-amyloid (1-42). J. Royal Soc. Interface 11, 20140165 (2014)Google Scholar
- 20.Tahirbegi, I.B., Pardo, W.A., Alvira, M., Mir, M., Samitier, J.: Amyloid Aβ 42, a promoter of magnetite nanoparticle formation in Alzheimer’s disease. Nanotechnology 27, 465102 (2016)Google Scholar
- 23.Vassar, P.S., Culling, C.F.: Fluorescent stains, with special reference to amyloid and connective tissues. Arch. Pathol. 68, 487–498 (1959)Google Scholar
- 24.LeVine III, H.: Thioflavine T interaction with synthetic Alzheimer's disease β-amyloid peptides: detection of amyloid aggregation in solution. Protein Sci. 2, 404–410 (1993)Google Scholar
- 25.Huang, X., Atwood, C.S., Hartshorn, M.A., Multhaup, G., Goldstein, L.E., Scarpa, R.C., Cuajungco, M.P., Gray, D.N., Lim, J., Moir, R.D., Tanzi, R.E., Bush, A.I.: The Aβ peptide of Alzheimer’s disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry 38, 7609–7616 (1999)Google Scholar