title: Extension of the generic amyloid hypothesis to nonproteinaceous metabolite assemblies.
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.
authors.affiliation: Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Shira
authors.initials: S
authors.lastname: Shaham-Niv
authors.affiliation: Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel. ; Department of Oral Biology, The Goldschleger School of Dental Medicine, Tel Aviv Univeristy, Tel Aviv 69978, Israel.
authors.forename: Lihi
authors.initials: L
authors.lastname: Adler-Abramovich
authors.affiliation: Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Lee
authors.initials: L
authors.lastname: Schnaider
authors.affiliation: Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel. ; Department of Materials Science and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Ehud
authors.initials: E
authors.lastname: Gazit
keywords: Amyloid Formation; Amyloid hypothesis; Metabolic disorders; Nano-assemblies; Nanoscience; molecular recognition; nanotechnology; self-assembly