| Autor: |
Zhi-Wen Hu, Vugmeyster, Liliya, Dan Fai Au, Ostrovsky, Dmitry, Yan Sun, Wei Qiang |
| Předmět: |
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| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America; 6/4/2019, Vol. 116 Issue 23, p11253-11258, 6p |
| Abstrakt: |
The structural polymorphism in β-amyloid (Aβ) plaques from Alzheimer disease (AD) has been recognized as an important pathological factor. Plaques from sporadic AD patients contain fibrillar deposits of various amyloid proteins/peptides, including posttranslational modified Aβ (PTM-Aβ) subtypes. Although many PTM-Aβs were shown to accelerate the fibrillation process, increase neuronal cytotoxicity of aggregates, or enhance the stability of fibrils, the contribution of PTM-Aβs to structural polymorphisms and their pathological roles remains unclear. We report here the NMR-based structure for the Ser-8-phosphorylated 40-residue Aβ (pS8-Aβ40) fibrils, which shows significant difference to the wild-type fibrils, with higher cross-seeding efficiency and thermodynamic stability. Given these physicochemical properties, the structures originated from pS8-Aβ40 fibrils may potentially dominate the polymorphisms in the mixture of wild-type and phosphorylated Aβ deposits. Our results imply that Aβ subtypes with "seeding-prone" properties may influence the polymorphisms of amyloid plaques through the crossseeding process. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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