Neurotoxic, redox-competent Alzheimer's --amyloid is released from lipid membrane by methionine oxidation

Barnham, Kevin J., Ciccotosto, Giuseppe D., Tickler, Anna K., Ali, Feda E., Smith, Danielle G., Williamson, Nicholas A., Lam, Yuen-Han, Carrington, Darryl, Tew, Deborah, Kocak, Gulcan, Volitakis, Irene, Separovic, Frances, Barrow, Colin J., Wade, John D., Masters, Colin L., Cherny, Robert A., Curtain, Cyril C., Bush, Ashley I. and Cappai, Roberto 2003, Neurotoxic, redox-competent Alzheimer's --amyloid is released from lipid membrane by methionine oxidation, Journal of biological chemistry, vol. 278, no. 44, pp. 42959-42965, doi: 10.1074/jbc.M305494200.

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Title Neurotoxic, redox-competent Alzheimer's --amyloid is released from lipid membrane by methionine oxidation
Author(s) Barnham, Kevin J.
Ciccotosto, Giuseppe D.
Tickler, Anna K.
Ali, Feda E.
Smith, Danielle G.
Williamson, Nicholas A.
Lam, Yuen-Han
Carrington, Darryl
Tew, Deborah
Kocak, Gulcan
Volitakis, Irene
Separovic, Frances
Barrow, Colin J.ORCID iD for Barrow, Colin J.
Wade, John D.
Masters, Colin L.
Cherny, Robert A.
Curtain, Cyril C.
Bush, Ashley I.
Cappai, Roberto
Journal name Journal of biological chemistry
Volume number 278
Issue number 44
Start page 42959
End page 42965
Publisher American Society for Biochemistry and Molecular Biology
Place of publication Bethesda, Md.
Publication date 2003-10-31
ISSN 0021-9258
Summary The amyloid β peptide is toxic to neurons, and it is believed that this toxicity plays a central role in the progression of Alzheimer's disease. The mechanism of this toxicity is contentious. Here we report that an Aβ peptide with the sulfur atom of Met-35 oxidized to a sulfoxide (Met(O)Aβ) is toxic to neuronal cells, and this toxicity is attenuated by the metal chelator clioquinol and completely rescued by catalase implicating the same toxicity mechanism as reduced Aβ. However, unlike the unoxidized peptide, Met(O)Aβ is unable to penetrate lipid membranes to form ion channel-like structures, and β-sheet formation is inhibited, phenomena that are central to some theories for Aβ toxicity. Our results show that, like the unoxidized peptide, Met(O)Aβ will coordinate Cu2+ and reduce the oxidation state of the metal and still produce H2O2. We hypothesize that Met(O)Aβ production contributes to the elevation of soluble Aβ seen in the brain in Alzheimer's disease.
Language eng
DOI 10.1074/jbc.M305494200
Field of Research 060110 Receptors and Membrane Biology
110106 Medical Biochemistry: Proteins and Peptides (incl Medical Proteomics)
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2003, American Society for Biochemistry and Molecular Biology
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Document type: Journal Article
Collection: School of Life and Environmental Sciences
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