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Updated: Jul 4, 2026

Rapid Generation of Amyloid from Native Proteins In vitro
Published on: December 5, 2013
Serpins show structural basis for oligomer toxicity and amyloid ubiquity
Robin W Carrell1, Alec Mushunje, Aiwu Zhou
1Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK. rwc1000@cam.ac.uk
Abstract:
Many disorders, including Alzheimer's, the prion encephalopathies and other neurodegenerative diseases, result from aberrant protein aggregation. Surprisingly, cellular toxicity is often due not to the highly-ordered aggregates but to the oligomers that precede their formation. Using serpins as a paradigm, we show how the active and infective interface of oligomers is inherently toxic and can promiscuously bind to unrelated peptides, including neurotransmitters. Extension of the oligomer and its eventual sequestration as amyloid can thus be seen as a protective response to block the toxic interface. We illustrate how the preferential self-association that gives this protection has been selectively favoured.
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