Monomer-dependent secondary nucleation in amyloid formation

被引：110
作者：
Linse S. [1 ]
机构：
[1] Chemical Centre, Biochemistry & Structural Biology, Lund University, P O Box 124, Lund
来源：
Biophysical Reviews | 2017年 / 9卷 / 4期
基金：
欧洲研究理事会;
关键词：
Amyloid formation; Inhibitors; Monomers; Secondary nucleation; Therapeutic developments;
D O I：
10.1007/s12551-017-0289-z
中图分类号：
学科分类号：
摘要：
Secondary nucleation of monomers on the surface of an already existing aggregate that is formed from the same kind of monomers may lead to autocatalytic amplification of a self-assembly process. Such monomer-dependent secondary nucleation occurs during the crystallization of small molecules or proteins and self-assembled materials, as well as in protein self-assembly into fibrous structures. Indications of secondary nucleation may come from analyses of kinetic experiments starting from pure monomers or monomers supplemented with a low concentration of pre-formed aggregates (seeds). More firm evidence requires additional experiments, for example those employing isotope labels to distinguish new aggregates arising from the monomer from those resulting from fragmentation of the seed. In cases of amyloid formation, secondary nucleation leads to the formation of toxic oligomers, and inhibitors of secondary nucleation may serve as starting points for therapeutic developments. Secondary nucleation displays a high degree of structural specificity and may be enhanced by mutations or screening of electrostatic repulsion. © 2017, The Author(s).
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页码：329 / 338
页数：9
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