Molecular mechanism of alpha-synuclein aggregation in Lewy body disease

2015 Fiscal Year Final Research Report

• Project/Area Number: 24300131
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Hirosaki University
• Principal Investigator: Wakabayashi Koichi 弘前大学, 医学(系)研究科(研究院), 教授 (50240768)
• Co-Investigator(Kenkyū-buntansha): TANJI Kunikazu 弘前大学, 大学院医学研究科, 助教 (10271800) ; MIKI Yasuo 弘前大学, 大学院医学研究科, 助教 (30709142) ; MORI Fumiaki 弘前大学, 大学院医学研究科, 准教授 (60200383)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Keywords: パーキンソン病 / レビー小体 / オートファジー

Outline of Final Research Achievements

In Lewy body disease (LBD), insoluble alpha-synuclein (AS) is widely deposited in the presynaptic terminals as well as in the neuronal cytoplasm. To test the possibility that activated autophagy can degrade abnormal molecules, we investigated the effect of trehalose on abnormal aggregation of AS in a model of LBD. Trehalose is a natural disaccharide composed of two glucose units. 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 AS was suppressed in mice following oral administration of trehalose, despite an apparent alteration was not observed regarding abnormal aggregation of AS. These results suggest that oral intake of trehalose modulates propensity of molecules prior to aggregation formation.

Free Research Field

神経病理学