Publikation:

Attenuated amyloid-β aggregation and neurotoxicity owing to methionine oxidation

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Datum

2007

Autor:innen

Johansson, Ann-Sofi
Bergquist, Jonas
Volbracht, Christiane
Päiviö, Anna
Leist, Marcel
Lannfelt, Lars
Westlind-Danielsson, Anita

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Neuroreport. 2007, 18(6), pp. 559-563. ISSN 0959-4965. eISSN 1473-558X. Available under: doi: 10.1097/WNR.0b013e3280b07c21

Zusammenfassung

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.

Zusammenfassung in einer weiteren Sprache

Fachgebiet (DDC)
570 Biowissenschaften, Biologie

Schlagwörter

amyloid-β, methionine 35, neurotoxicity, oligomers, oxidation, protofibrils

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ISO 690JOHANSSON, 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. 2007, 18(6), pp. 559-563. ISSN 0959-4965. eISSN 1473-558X. Available under: doi: 10.1097/WNR.0b013e3280b07c21
BibTex
@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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