Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 465, Issue 4, Pages 746-752Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2015.08.076
Keywords
Autophagy; LC3; Lewy body disease; Trehalose; alpha-Synuclein; Chaperone
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Funding
- JSPS KAKENHI [23500425, 26860655, 23500424, 24300131]
- Hirosaki University Institutional Research Grant
- Research Committee for Ataxic Disease
- Ministry of Health, Labor and Welfare, Japan
- Japan Foundation for neuroscience and Mental Health
- Grants-in-Aid for Scientific Research [26860655, 23500425, 26430049, 23500424] Funding Source: KAKEN
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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 a-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 a-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 a-synuclein was suppressed in mice following oral administration of trehalose, despite an apparent alteration was not observed regarding abnormal aggregation of a-synuclein. These results suggest that the oral intake of trehalose modulates propensity of molecules prior to aggregation formation. (C) 2015 Elsevier Inc. All rights reserved.
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