Phenylalanine assembly into toxic fibrils suggests amyloid etiology in phenylketonuria

TitlePhenylalanine assembly into toxic fibrils suggests amyloid etiology in phenylketonuria
Publication TypeJournal Article
Year of Publication2012
AuthorsAdler-Abramovich L., Vaks L., Carny O., Trudler D., Magno A., Caflisch A., Frenkel D., Gazit E.
JournalNature Chemical Biology
Date Published2012 Aug
Type of ArticleResearch Article
KeywordsAmyloid, Animals, Antibodies, Biophysics, CHO Cells, Cricetinae, Hippocampus, Humans, Immunoprecipitation, Mice, Models, Molecular, Parietal Lobe, Phenylalanine, Phenylketonurias, Protein Conformation, Rabbits

Phenylketonuria (PKU) is characterized by phenylalanine accumulation and progressive mental retardation caused by an unknown mechanism. We demonstrate that at pathological concentrations, phenylalanine self-assembles into fibrils with amyloid-like morphology and well-ordered electron diffraction. These assemblies are specifically recognized by antibodies, show cytotoxicity that can be neutralized by the antibodies and are present in the hippocampus of model mice and in parietal cortex brain tissue from individuals with PKU. This is, to our knowledge, the first demonstration that a single amino acid can form amyloid-like deposits, suggesting a new amyloidosis-like etiology for PKU.



Alternate JournalNat. Chem. Biol.
PubMed ID22706200