Phenylalanine assembly into toxic fibrils suggests amyloid etiology in phenylketonuria.

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.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

Adler-Abramovich L,Vaks L,Carny O,Trudler D,Magno A,Caflisch A,Frenkel D,Gazit E

doi

10.1038/nchembio.1002

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

701-6

issue

8

eissn

1552-4450

issn

1552-4469

pii

nchembio.1002

journal_volume

8

pub_type

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