Role of the region 23-28 in Aβ fibril formation:: Insights from simulations of the monomers and dimers of Alzheimer's peptides Aβ40 and Aβ42

被引：83
作者：
Melquiond, Adrien [1 ,2 ]
Dong, Xiao [1 ,2 ,3 ]
Mousseau, Normand [3 ]
Derreumaux, Philippe [1 ,2 ]
机构：
[1] Inst Biol Physicochim, CNRS, UPR9080, Lab Biochim Theor, F-75005 Paris, France
[2] Univ Paris 07, F-75005 Paris, France
[3] Univ Montreal, Dept Phys & Regroupement Quebecois Mat Pointe, Montreal, PQ, Canada
来源：
CURRENT ALZHEIMER RESEARCH | 2008年 / 5卷 / 03期
关键词：
protein aggregation; simulations; Amyloid-beta; Alzheimer; coarse-grained model; structures; thermodynamics; monomer and dimer;
D O I：
10.2174/156720508784533330
中图分类号：
R74 [神经病学与精神病学];
学科分类号：
摘要：
Self-assembly of the 40/42 amino acid A beta peptide is a key player in Alzheimer's disease. A beta 40 is the most prevalent species, while A beta 42 is the most toxic. It has been suggested that the amino acids 21-30 could nucleate the folding of A beta monomer and a bent in this region could be the rate-limiting step in A beta fibril formation. In this study, we review our current understanding of the computer-predicted conformations of amino acids 23-28 in the monomer of A beta(21-30) and the monomers A beta 40 and A beta 42. On the basis of new simulations on dimers of full-length A beta, we propose that the rate-limiting step involves the formation of a multimeric beta-sheet spanning the central hydrophobic core ( residues 17-21).
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收藏
页码：244 / 250
页数：7
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