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Phenylalanine assembly into toxic fibrils suggests amyloid etiology in phenylketonuria


Adler-Abramovich, Lihi; Vaks, Lilach; Carny, Ohad; Trudler, Dorit; Magno, Andrea; Caflisch, Amedeo; Frenkel, Dan; Gazit, Ehud (2012). Phenylalanine assembly into toxic fibrils suggests amyloid etiology in phenylketonuria. Nature Chemical Biology, 8(8):701-706.

Abstract

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.

Abstract

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:2012
Deposited On:09 Oct 2012 15:20
Last Modified:05 Apr 2016 15:59
Publisher:Nature Publishing Group
ISSN:1552-4450
Publisher DOI:https://doi.org/10.1038/nchembio.1002
PubMed ID:22706200

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