Neurotoxic protein oligomers - what you see is not always what you get

An increasing body of evidence suggests that soluble assemblies of amyloid proteins are the predominant neurotoxic species in many amyloid-related diseases. Consequently, the focus of research on pathologic mechanisms underlying amyloidoses has shifted from amyloid fibrils to oligomers. Biophysical...

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Bibliographic Details
Published in:Amyloid 2005-06, Vol.12 (2), p.88-95
Main Authors: Bitan, Gal, Fradinger, Erica A, Spring, Sean M, Teplow, David B
Format: Article
Language:English
Subjects:
Amyloid
Biopolymers - chemistry
Biopolymers - toxicity
Chromatography, Gel
Electrophoresis, Polyacrylamide Gel
Molecular Weight
Nervous System - drug effects
oligomer
Proteins - chemistry
Proteins - toxicity
protofibril
SDS-PAGE
Terminology as Topic
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Summary:An increasing body of evidence suggests that soluble assemblies of amyloid proteins are the predominant neurotoxic species in many amyloid-related diseases. Consequently, the focus of research on pathologic mechanisms underlying amyloidoses has shifted from amyloid fibrils to oligomers. Biophysical characterization of oligomers is difficult due to their metastable nature. The most popular experimental method for detection of oligomers has been SDS-PAGE. However, we provide experimental evidence that SDS-PAGE is not a reliable method for characterization of amyloid protein oligomers and discuss alternative approaches. In addition, we discuss how inconsistent nomenclature has obfuscated our understanding of the process and products of protein assembly. The goals of this paper are to identify pitfalls associated with the methods and language used to study protein oligomers and to provide alternatives, thereby facilitating successful elucidation of the mechanisms controlling amyloid protein oligomer assembly and toxicity.
ISSN:1350-6129
1744-2818
DOI:10.1080/13506120500106958