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Updated: Aug 29, 2026

Measuring RAN Peptide Toxicity in C. elegans
Published on: April 30, 2020
An aggregate-prone conformational epitope in trinucleotide repeat diseases
Keizo Sugaya1, Shiro Matsubara, Kazuhito Miyamoto
1Department of Neuroimaging, Tokyo Metropolitan Neurological Hospital, Japan. keizo_su@yahoo.co.jp
Abstract:
A broad range of neurodegenerative disorders is associated with accumulation of misfolded protein that is toxic to the cells. Knowledge of the conformational structure of the protein implicated is essential for understanding how an aggregate-prone protein causes disease. Here we show that a conformational epitope associated with aggregation property and cell toxicity is preserved in homopolymeric amino acid stretches implicated in oculopharyngeal muscular dystrophy (OPMD) and polyglutamine diseases. These disorders are characterized by the nuclear inclusions and a genetic gain of function. This is the first report of a candidate pathogenic structure, which may trigger aggregation of the proteins in trinucleotide repeat diseases including OPMD and polyglutamine diseases. It provides a possible therapeutic target useful for these disorders.
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