Melquiond Adrien, Dong Xiao, Mousseau Normand, Derreumaux Philippe
Laboratoire de Biochimie Théorique, UPR9080 CNRS, Institut de Biologie Physico-Chimique et Université Paris 7 Denis-Diderot, Paris, France.
Curr Alzheimer Res. 2008 Jun;5(3):244-50. doi: 10.2174/156720508784533330.
Self-assembly of the 40/42 amino acid Abeta peptide is a key player in Alzheimer's disease. Abeta40 is the most prevalent species, while Abeta42 is the most toxic. It has been suggested that the amino acids 21-30 could nucleate the folding of Abeta monomer and a bent in this region could be the rate-limiting step in Abeta fibril formation. In this study, we review our current understanding of the computer-predicted conformations of amino acids 23-28 in the monomer of Abeta(21-30) and the monomers Abeta40 and Abeta42. On the basis of new simulations on dimers of full-length Abeta, we propose that the rate-limiting step involves the formation of a multimeric beta-sheet spanning the central hydrophobic core (residues 17-21).
40/42个氨基酸的β-淀粉样肽（Aβ）的自组装是阿尔茨海默病的关键因素。Aβ40是最常见的类型，而Aβ42毒性最强。有人提出，21-30位氨基酸可能引发Aβ单体的折叠，该区域的一个弯曲可能是Aβ纤维形成的限速步骤。在本研究中，我们回顾了目前对Aβ（21-30）单体以及Aβ40和Aβ42单体中23-28位氨基酸的计算机预测构象的理解。基于对全长Aβ二聚体的新模拟，我们提出限速步骤涉及跨越中央疏水核心（17-21位残基）的多聚体β-折叠的形成。
