期刊
ELIFE
卷 2, 期 -, 页码 -出版社
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.00857
关键词
-
类别
资金
- National Institutes of Health [AG029430]
- US Department of Energy [DE-FC02-02ER63421]
- U.S. Department of Energy (DOE) [DE-FC02-02ER63421] Funding Source: U.S. Department of Energy (DOE)
Amyloid protein aggregates are associated with dozens of devastating diseases including Alzheimer's, Parkinson's, ALS, and diabetes type 2. While structure-based discovery of compounds has been effective in combating numerous infectious and metabolic diseases, ignorance of amyloid structure has hindered similar approaches to amyloid disease. Here we show that knowledge of the atomic structure of one of the adhesive, steric-zipper segments of the amyloid-beta (A beta) protein of Alzheimer's disease, when coupled with computational methods, identifies eight diverse but mainly flat compounds and three compound derivatives that reduce A beta cytotoxicity against mammalian cells by up to 90%. Although these compounds bind to A beta fibers, they do not reduce fiber formation of A beta. Structure-activity relationship studies of the fiber-binding compounds and their derivatives suggest that compound binding increases fiber stability and decreases fiber toxicity, perhaps by shifting the equilibrium of A beta from oligomers to fibers.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据