Fibrillar seeds alleviate amyloid-β cytotoxicity by omitting formation of higher-molecular-weight oligomers
| Autor: | Jun-Jie Luo, Ji-Sheng Yu, Yufen Zhao, Qian Liu, Wei-Hui Wu, Ye-ping Yu, Jia Hu, De-Sheng Zhao, Yan-Mei Li, Xun Sun, Zhi-Wu Yu |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Neurons
Amyloid beta-Peptides Cell Survival Size-exclusion chromatography Biophysics food and beverages Isothermal titration calorimetry Cell Biology Fibril Biochemistry Oligomer Cell Line chemistry.chemical_compound Monomer Solubility chemistry Alzheimer Disease Animals Humans Cytotoxicity Molecular Biology Polyacrylamide gel electrophoresis Fetal bovine serum |
| Zdroj: | Biochemical and Biophysical Research Communications. 439:321-326 |
| ISSN: | 0006-291X |
| Popis: | Amyloid-β (Aβ) peptides can exist in distinct forms including monomers, oligomers and fibrils, consisting of increased numbers of monomeric units. Among these, Aβ oligomers are implicated as the primary toxic species as pointed by multiple lines of evidence. It has been suggested that toxicity could be rendered by the soluble higher-molecular-weight (high-n) Aβ oligomers. Yet, the most culpable form in the pathogenesis of Alzheimer’s disease (AD) remains elusive. Moreover, the potential interaction among the insoluble fibrils that have been excluded from the responsible aggregates in AD development, Aβ monomers and high-n oligomers is undetermined. Here, we report that insoluble Aβ fibrillar seeds can interact with Aβ monomers at the stoichiometry of 1:2 (namely, each Aβ molecule of seed can bind to two Aβ monomers at a time) facilitating the fibrillization by omitting the otherwise mandatory formation of the toxic high-n oligomers during the fibril maturation. As a result, the addition of exogenous Aβ fibrillar seeds is seen to rescue neuronal cells from Aβ cytotoxicity presumably exerted by high-n oligomers, suggesting an unexpected protective role of Aβ fibrillar seeds. |
| Databáze: | OpenAIRE |
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