title: Trehalose intake induces chaperone molecules along with autophagy in a mouse model of Lewy body disease.
abstract: The accumulation of mis-folded and/or abnormally modified proteins is a major characteristic of many neurodegenerative diseases. In Lewy body disease (LBD), which includes Parkinson's disease and dementia with Lewy bodies, insoluble α-synuclein is widely deposited in the presynaptic terminals as well as in the neuronal cytoplasm in distinct brain regions. It is well known that the autophagy-lysosome system serves as an efficient degradation pathway for abnormal molecules within cells. To test the possibility that activated autophagy can degrade abnormal molecules, we investigated the effect of trehalose on abnormal aggregation of α-synuclein in a model of LBD. Trehalose is a natural disaccharide composed of two glucose units and functions as an autophagy inducer. Consistent with previous studies, trehalose increased level of the autophagosomal protein LC3, especially a lipidated form LC3-II in cultured cells and mice brain. Also, trehalose increased levels of several chaperon molecules, such as HSP90 and SigmaR1, in the brains of LBD model mice. Further studies revealed that level of detergent-insoluble α-synuclein was suppressed in mice following oral administration of trehalose, despite an apparent alteration was not observed regarding abnormal aggregation of α-synuclein. These results suggest that the oral intake of trehalose modulates propensity of molecules prior to aggregation formation.
authors: Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan. Electronic address: kunikazu@hirosaki-u.ac.jp.
authors: Kunikazu
authors: K
authors: Tanji
authors: Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors: Yasuo
authors: Y
authors: Miki
authors: Department of Stress Response Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors: Atsushi
authors: A
authors: Maruyama
authors: Department of Stress Response Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors: Junsei
authors: J
authors: Mimura
authors: Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors: Tomoh
authors: T
authors: Matsumiya
authors: Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors: Fumiaki
authors: F
authors: Mori
authors: Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors: Tadaatsu
authors: T
authors: Imaizumi
authors: Department of Stress Response Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors: Ken
authors: K
authors: Itoh
authors: Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors: Koichi
authors: K
authors: Wakabayashi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis; D006367:HeLa Cells; D006801:Humans; D020961:Lewy Body Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008320:Maltose / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D018832:Molecular Chaperones / Q000096:biosynthesis*; D066263:Protein Aggregation, Pathological / Q000517:prevention & control; D017480:Receptors, sigma / Q000096:biosynthesis; D012995:Solubility; D014199:Trehalose / Q000008:administration & dosage*; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism; D000097605:Sigma-1 Receptor
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D018841:HSP90 Heat-Shock Proteins; D008320:Maltose; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones; D017480:Receptors, sigma; D014199:Trehalose; D051844:alpha-Synuclein; D000097605:Sigma-1 Receptor; C115010:Becn1 protein, mouse; C480860:Map1lc3b protein, mouse
keywords: Autophagy; Chaperone; LC3; Lewy body disease; Trehalose; α-Synuclein