期刊
PLOS ONE
卷 8, 期 11, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0080262
关键词
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资金
- PEPS IDEX
- JSPS KAKENHI [24570143]
- RIKEN
- Grants-in-Aid for Scientific Research [24570143] Funding Source: KAKEN
Amyloid beta (A beta) peptides produced by APP cleavage are central to the pathology of Alzheimer's disease. Despite widespread interest in this issue, the relationship between the auto-assembly and toxicity of these peptides remains controversial. One intriguing feature stems from their capacity to form anti-parallel beta-sheet oligomeric intermediates that can be converted into a parallel topology to allow the formation of protofibrillar and fibrillar A beta. Here, we present a novel approach to determining the molecular aspects of A beta assembly that is responsible for its in vivo toxicity. We selected A beta mutants with varying intracellular toxicities. In vitro, only toxic A beta (including wild-type A beta(42)) formed urea-resistant oligomers. These oligomers were able to assemble into fibrils that are rich in anti-parallel beta-sheet structures. Our results support the existence of a new pathway that depends on the folding capacity of A beta.
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