Visualization of dendritic spine: Implication for neurodegenerative dementia

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15473
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Hirosaki University
• Principal Investigator: Wakabayashi Koichi 弘前大学, 医学研究科, 教授 (50240768)
• Co-Investigator(Kenkyū-buntansha): 丹治 邦和 弘前大学, 医学研究科, 助教 (10271800)
• Research Collaborator: 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): 2016-04-01 – 2018-03-31
• Keywords: シナプス蛋白 / 神経変性 / レビー小体病 / パーキンソン病 / 多系統萎縮症 / シヌクレイン / オートファジー

Outline of Final Research Achievements

We have shown that autophagy was dysregulated in patients with alpha-synucleinopathy [Parkinson’s disease (PD), dementia with Lewy bodies and multiple system atrophy (MSA)]. Therefore, we elucidated the role of upstream proteins of autophagy in the pathogenesis of MSA. Our results demonstrated that AMBRA1 is a novel hub binding protein of alpha-synuclein and plays a central role in the pathogenesis of MSA through the degradative dynamics of alpha-synuclein. These results raise the possibility that molecular modulation targeting AMBRA1 can be a promising candidate for the treatment of alpha-synucleinopathy. We further performed whole transcriptome assay by microarray, quantitative RT-PCR and Western blot analysis using peripheral blood mononuclear cells (PBMCs) of patients with PD and age-matched controls. We provided evidence that autophagy in PBMCs could detect a feature confirmed by neuropathology of PD and this alteration of autophagy is a fundamental aspect of PD.

Free Research Field

脳神経病理学