Research ArticleBIOLOGICAL CHEMISTRY

Extension of the generic amyloid hypothesis to nonproteinaceous metabolite assemblies

Science Advances  14 Aug 2015:
Vol. 1, no. 7, e1500137
DOI: 10.1126/sciadv.1500137

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Abstract

The accumulation of amyloid fibrils is the hallmark of several major human diseases. Although the formation of these supramolecular entities has previously been associated with proteins and peptides, it was later demonstrated that even phenylalanine, a single amino acid, can form fibrils that have amyloid-like biophysical, biochemical, and cytotoxic properties. Moreover, the generation of antibodies against these assemblies in phenylketonuria patients and the correlating mice model suggested a pathological role for the assemblies. We determine that several other metabolites that accumulate in metabolic disorders form ordered amyloid-like ultrastructures, which induce apoptotic cell death, as observed for amyloid structures. The formation of amyloid-like assemblies by metabolites implies a general phenomenon of amyloid formation, not limited to proteins and peptides, and offers a new paradigm for metabolic diseases.

Keywords
  • Amyloid Formation
  • self-assembly
  • Metabolic disorders
  • molecular recognition
  • Amyloid hypothesis
  • Nano-assemblies
  • nanotechnology
  • Nanoscience

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

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