title: An aggregate-prone conformational epitope in trinucleotide repeat diseases.
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.
authors.affiliation: Department of Neuroimaging, Tokyo Metropolitan Neurological Hospital, Japan. keizo_su@yahoo.co.jp
authors.forename: Keizo
authors.initials: K
authors.lastname: Sugaya
authors.forename: Shiro
authors.initials: S
authors.lastname: Matsubara
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kawata
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D019556:COS Cells; D002449:Cell Aggregation / Q000235:genetics; D002522:Chlorocebus aethiops; D000939:Epitopes / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D002479:Inclusion Bodies / Q000235:genetics / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D039141:Muscular Dystrophy, Oculopharyngeal / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D010455:Peptides / Q000235:genetics; D011487:Protein Conformation; D018911:Trinucleotide Repeats / Q000235:genetics*
chemical_list: D000939:Epitopes; D010455:Peptides; C097188:polyglutamine