| 1. |
- Johansson, Ann-Sofi, et al.
(author)
-
Attenuated amyloid-β aggregation and neurotoxicity owing to methionine oxidation
- 2007
-
In: NeuroReport. - 0959-4965 .- 1473-558X. ; 18:6, s. 559-563
-
Journal article (peer-reviewed)abstract
- Aggregation of the amyloid-beta (Abeta) peptide into amyloid plaques is a characteristic feature of Alzheimer's disease neuropathogenesis. We and others have previously demonstrated delayed Abeta 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 Abeta1-42 and Abeta1-40Arctic 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 Abeta1-42 and Abeta1-40Arctic 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 Abeta1-42 and Abeta1-40Arctic, and thereby reduces neurotoxicity.
|
|
| 2. |
- Palmblad, Magnus, et al.
(author)
-
Oxidation of Methionine-35 Attenuates Formation of Amyloid β-Peptide 1-40 Oligomers
- 2002
-
In: Journal of chemical biology. - 1864-6158 .- 1864-6166. ; 23:1, s. S397-S397
-
Journal article (peer-reviewed)abstract
- Amyloid plaques formed by aggregation of the amyloid β-peptide (Aβ) are an intrinsic component of Alzheimer disease pathogenesis. It has been suggested that oxidation of methionine 35 in Aβ has implications for Alzheimer disease, and it has been shown that oxidation of Met-35 significantly inhibits aggregation in vitro. In this study, the aggregational properties of Aβ-(1–40) before and after Met-35 oxidation were investigated using electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. The results show that Aβ-(1–40)Met-35(O) trimer and tetramer formation is significantly attenuated as compared with Aβ-(1–40). This suggests that oxidation of Met-35 inhibits a conformational switch in Aβ-(1–40) necessary for trimer but not dimer formation. Random incorporation of Aβ-(1–40) and Aβ-(1–40)Met-35(O) in homo- and heterooligomers could also be observed. This is the first report of an early rate-limiting step in Aβ-(1–40) aggregation. Slowing of the fibrillization process at this early step is likely to support prolonged solubility and clearance of Aβ from brain and may reduce disease progression.
|
|
| 3. |
|
|
