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Monomer-dependent secondary nucleation in amyloid formation

Linse, Sara LU (2017) In Biophysical Reviews 9(4). p.329-338
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Amyloid formation, Inhibitors, Monomers, Secondary nucleation, Therapeutic developments
in
Biophysical Reviews
volume
9
issue
4
pages
10 pages
publisher
Springer Verlag
external identifiers
  • scopus:85028631714
ISSN
1867-2450
DOI
10.1007/s12551-017-0289-z
language
English
LU publication?
yes
id
7fe4b0d3-df2a-40f6-ba40-aee1f7eb915d
date added to LUP
2017-09-27 11:08:25
date last changed
2018-09-02 04:41:42
@article{7fe4b0d3-df2a-40f6-ba40-aee1f7eb915d,
  abstract     = {<p>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.</p>},
  author       = {Linse, Sara},
  issn         = {1867-2450},
  keyword      = {Amyloid formation,Inhibitors,Monomers,Secondary nucleation,Therapeutic developments},
  language     = {eng},
  month        = {08},
  number       = {4},
  pages        = {329--338},
  publisher    = {Springer Verlag},
  series       = {Biophysical Reviews},
  title        = {Monomer-dependent secondary nucleation in amyloid formation},
  url          = {http://dx.doi.org/10.1007/s12551-017-0289-z},
  volume       = {9},
  year         = {2017},
}