| 1. |
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| 2. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
- Cukalevski, Risto, et al.
(författare)
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Role of Aromatic Side Chains in Amyloid β-Protein Aggregation.
- 2012
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Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 3:12, s. 1008-1016
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Tidskriftsartikel (refereegranskat)abstract
- Aggregation of the amyloid β-protein (Aβ) is believed to be involved in Alzheimer's disease pathogenesis. Here we have investigated the importance of the aromatic rings at positions 19 and 20 for the aggregation rate and mechanism by substituting phenylalanine with leucine. Aggregation kinetics were monitored as a function of time and peptide concentration by thioflavin T (ThT) fluorescence, the aggregation equilibrium by sedimentation assay, structural changes using circular dichroism spectroscopy and the presence of fibrillar material was detected with cryo-transmission electron microscopy. All peptides convert from monomer to amyloid fibrils in a concentration-dependent manner. Substituting F19 with leucine results in a peptide that aggregates significantly slower than the wild type, while substitution of F20 produces a peptide that aggregates faster. The effects of the two substitutions are additive, since simultaneous substitution of F19 and F20 produces a peptide with aggregation kinetics intermediate between F19L and F20L. Our results suggest that the aromatic side-chain of F19 favors nucleation of the aggregation process and may be an important target for therapeutic intervention.
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| 5. |
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| 6. |
- Hellstrand, Erik, et al.
(författare)
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Amyloid beta-Protein Aggregation Produces Highly Reproducible Kinetic Data and Occurs by a Two-Phase Process
- 2010
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Ingår i: ACS Chemical Neuroscience. - : American Chemical Society (ACS). - 1948-7193. ; 1:1, s. 13-18
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Tidskriftsartikel (refereegranskat)abstract
- Protein aggregation can lead to major disturbances of cellular processes and is associated with several diseases. We report kinetic and equilibrium data by ThT fluorescence and enzyme-linked immunosorbent assay of sufficient quality and reproducibility to form a basis for mechanistic understanding of amyloid beta-peptide (A beta) fibril formation. Starting from monomeric peptide in a pure buffer system without cosolvents, we find that the kinetics of A beta aggregation vary strongly with peptide concentration in a highly predictable manner. The free A beta concentration in equilibrium with fibrils was found to vary with total peptide concentration in a manner expected for a two-phase system. The free versus total A beta concentration was linear up to ca. 0.2,mu M, after which free A beta decreased with total A beta toward an asymptotic value. Our results imply that A beta fibril formation arises from a sequence of events in a highly predictable manner.
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| 7. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 8. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 9. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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