期刊
FEBS LETTERS
卷 591, 期 5, 页码 822-830出版社
WILEY
DOI: 10.1002/1873-3468.12590
关键词
Alzheimer's disease; amyloid fibril; amyloid-beta; control; cytotoxicity; self-assembly
资金
- Medical research council UK [MR/K022105/1]
- University of Sussex
- Alzheimer's society
- Alzheimer's research UK
- BBSRC [BB/E009042/1] Funding Source: UKRI
- MRC [MR/K022105/1] Funding Source: UKRI
- Alzheimers Research UK [ART-PG2007-3] Funding Source: researchfish
- Biotechnology and Biological Sciences Research Council [BB/E009042/1] Funding Source: researchfish
- Medical Research Council [MR/K022105/1] Funding Source: researchfish
beta-amyloid 1-42 (A beta 1-42) is a self-assembling peptide that goes through many conformational and morphological changes before forming the fibrils that are deposited in extracellular plaques characteristic of Alzheimer's disease. The link between A beta 1-42 structure and toxicity is of major interest, in particular, the neurotoxic potential of oligomeric species. Many studies utilise reversed (A beta 42-1) and scrambled (A beta S) forms of amyloid-beta as control peptides. Here, using circular dichroism, thioflavin T fluorescence and transmission electron microscopy, we reveal that both control peptides self-assemble to form fibres within 24 h. However, oligomeric A beta reduces cell survival of hippocampal neurons, while A beta 42-1 and Abs have reduced effect on cellular health, which may arise from their ability to assemble rapidly to form protofibrils and fibrils.
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