Oligomeric intermediates in amyloid formation: structure determination and mechanisms of toxicity

Marcus Fändrich

doi:10.1016/j.jmb.2012.01.006

Oligomeric intermediates in amyloid formation: structure determination and mechanisms of toxicity

J Mol Biol. 2012 Aug 24;421(4-5):427-40. doi: 10.1016/j.jmb.2012.01.006. Epub 2012 Jan 12.

Author

Marcus Fändrich¹

Affiliation

¹ Max-Planck Research Unit for Enzymology of Protein Folding and Martin Luther University Halle-Wittenberg, Weinbergweg 22, 01620 Halle (Saale), Germany. [email protected]

PMID: 22248587
DOI: 10.1016/j.jmb.2012.01.006

Abstract

Oligomeric intermediates are non-fibrillar polypeptide assemblies that occur during amyloid fibril formation and that are thought to underlie the aetiology of amyloid diseases, such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Focusing primarily on the oligomeric states formed from Alzheimer's disease β-amyloid (Aβ) peptide, this review will make references to other polypeptide systems, highlighting common principles or sequence-specific differences. The covered topics include the structural properties and polymorphism of oligomers, the biophysical mechanism of peptide self-assembly and its role for pathogenicity in amyloid disease. Oligomer-dependent toxicity mechanisms will be explained along with recently emerging possibilities of interference.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Alzheimer Disease / pathology
Alzheimer Disease / physiopathology
Amyloid / chemistry*
Amyloid / metabolism*
Amyloid / toxicity
Humans
Protein Conformation
Protein Folding
Protein Multimerization*

Substances

Amyloid