tailieunhanh - Báo cáo khoa học: Amyloid oligomers: dynamics and toxicity in the cytosol and nucleus

The accumulation of misfolded proteins in the cytosol and nucleus of neuronal cells leads to neurodegenerative disorders. Polyglutamine diseases are caused by polyglutamine-expanded proteins, whereas mutations in superoxide dismutase 1 lead to amyotrophic lateral sclerosis. | ỊFEBS Journal MINIREVIEW Amyloid oligomers dynamics and toxicity in the cytosol and nucleus Akira Kitamura1 and Hiroshi Kubota2 1 Department of Molecular CellDynamics Faculty of Advanced Life Science Hokkaido University Kita-ku Sapporo Japan 2 Department of Life Science Faculty of Engineering and Resource Science Akita University Akita Japan Keywords live cell imaging misfolded protein molecular chaperone neurodegenerative disease neuronal cell death oligomer protein aggregation protein degradation protein interaction spectroscopic analysis Correspondence H. Kubota Department of Life Science Faculty of Engineering and Resource Science Akita University 1-1 Tegatagakuen-cho Akita 010-8502 Japan Fax 81 18 75 3053 Tel 81 18 75 3053 E-mail hkubota@ Received 4 September 2009 revised 29 November 2009 accepted 1 December 2010 doi The accumulation of misfolded proteins in the cytosol and nucleus of neuronal cells leads to neurodegenerative disorders. Polyglutamine diseases are caused by polyglutamine-expanded proteins whereas mutations in superoxide dismutase 1 lead to amyotrophic lateral sclerosis. These structurally unstable mutant species perturb essential interactions between normal proteins and tend to aggregate because of the presence of exposed hydrophobic surfaces. Accumulating evidence suggests that soluble species including misfolded monomers and oligomers are more toxic than large insoluble aggregates or inclusions. Spectroscopic analysis including fluorescence recovery after photobleaching and fluorescence loss in photobleaching in living cells revealed that protein aggregates of misfolded proteins are dynamic structures that interact with other proteins such as molecular chaperones. Fluorescence correlation spectroscopy analysis detected soluble oligomers aggregates of misfolded proteins in cell extracts. Fluorescence resonance energy transfer analysis supported the notion that soluble oligo-mers aggregates are