title: Analyzing the aggregation of polyglutamine-expansion proteins and its modulation by molecular chaperones.
abstract: Polyglutamine (polyQ)-expansion proteins cause protein aggregation in the cytosol and nucleus of neuronal cells, leading to neurodegenerative diseases. For example, expansion of the polyQ tract (>40 repeats) in huntingtin (htt) proteins leads to Huntington disease, while polyQ-expanded ataxins cause several types of ataxias. PolyQ-rich inclusions are found in neuronal cells of patients, suggesting that polyQ disease is caused by protein misfolding. However, the mechanisms by which polyQ-expansion proteins exert neuronal toxicity are largely unknown. Here, we review experimental procedures to analyze the roles of molecular chaperones in preventing polyQ aggregation and toxicity as well as to measure the characteristics and dynamics of polyQ aggregation, particularly focusing on cellular models and dynamic imaging of fluorescently-labeled polyQ-expansion proteins and their modulation by chaperones.
authors.affiliation: Department of Life Science, Faculty of Engineering and Resource Science, Akita University, 1-1 Tegatagakuen-cho, Akita 010-8502, Japan. hkubota@gipc.akita-u.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kubota
authors.forename: Akira
authors.initials: A
authors.lastname: Kitamura
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagata
mesh_terms: D002478:Cells, Cultured; D003001:Cloning, Molecular; D036681:Fluorescence Recovery After Photobleaching / Q000379:methods; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods; D005455:Fluorescent Antibody Technique / Q000379:methods; D006801:Humans; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000473:pathology; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D017510:Protein Folding; D013050:Spectrometry, Fluorescence / Q000379:methods
chemical_list: D018832:Molecular Chaperones; D010455:Peptides; C097188:polyglutamine