Phenylalanine assembly into toxic fibrils suggests amyloid etiology in phenylketonuria.
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.
Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
Lihi
L
Adler-Abramovich
Lilach
L
Vaks
Ohad
O
Carny
Dorit
D
Trudler
Andrea
A
Magno
Amedeo
A
Caflisch
Dan
D
Frenkel
Ehud
E
Gazit
D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D000906:Antibodies; D001703:Biophysics; D016466:CHO Cells; D006224:Cricetinae; D006624:Hippocampus; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008958:Models, Molecular; D010296:Parietal Lobe; D010649:Phenylalanine / Q000737:chemistry* / Q000378:metabolism*; D010661:Phenylketonurias / Q000378:metabolism*; D011487:Protein Conformation; D011817:Rabbits
D000682:Amyloid; D000906:Antibodies; D010649:Phenylalanine