Attenuated amyloid-β aggregation and neurotoxicity owing to methionine oxidation
Attenuated amyloid-β aggregation and neurotoxicity owing to methionine oxidation
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Date
2007
Authors
Johansson, Ann-Sofi
Bergquist, Jonas
Volbracht, Christiane
Päiviö, Anna
Lannfelt, Lars
Westlind-Danielsson, Anita
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Neuroreport ; 18 (2007), 6. - pp. 559-563. - ISSN 0959-4965. - eISSN 1473-558X
Abstract
Aggregation of the amyloid-β (Aβ) peptide into amyloid plaques is a characteristic feature of Alzheimer's disease neuropathogenesis. We and others have previously demonstrated delayed Aβ aggregation as a consequence of oxidizing a single methionine residue at position 35 (Met-35). Here, we examined the consequences of Met-35 oxidation on the extremely aggregation-prone peptides Aβ1-42 and Aβ1-40Arctic with respect to protofibril and oligomer formation as well as neurotoxicity. Size exclusion chromatography and mass spectrometry demonstrated that monomer/dimers prevailed over larger oligomers after oxidizing Met-35, and consequently protofibril formation and aggregation of both A[beta]1-42 and Aβ1-40Arctic were delayed. The oxidized peptides completely lacked neurotoxic effects in cortical neuronal cultures under these conditions, in contrast to the neurotoxic properties of the unoxidized peptides. We conclude that oxidation of Met-35 significantly attenuates aggregation of Aβ1-42 and Aβ1-40Arctic, and thereby reduces neurotoxicity.
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570 Biosciences, Biology
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amyloid-β, methionine 35, neurotoxicity, oligomers, oxidation, protofibrils
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JOHANSSON, Ann-Sofi, Jonas BERGQUIST, Christiane VOLBRACHT, Anna PÄIVIÖ, Marcel LEIST, Lars LANNFELT, Anita WESTLIND-DANIELSSON, 2007. Attenuated amyloid-β aggregation and neurotoxicity owing to methionine oxidation. In: Neuroreport. 18(6), pp. 559-563. ISSN 0959-4965. eISSN 1473-558X. Available under: doi: 10.1097/WNR.0b013e3280b07c21BibTex
@article{Johansson2007-04-16Atten-40765, year={2007}, doi={10.1097/WNR.0b013e3280b07c21}, title={Attenuated amyloid-β aggregation and neurotoxicity owing to methionine oxidation}, number={6}, volume={18}, issn={0959-4965}, journal={Neuroreport}, pages={559--563}, author={Johansson, Ann-Sofi and Bergquist, Jonas and Volbracht, Christiane and Päiviö, Anna and Leist, Marcel and Lannfelt, Lars and Westlind-Danielsson, Anita} }
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