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パーキンソン病とその類縁疾患 1
Parkinson's Disease and Related Disorders 1

開催日 2014/9/12
時間 17:10 - 18:10
会場 Room I(311+312)
Chairperson(s) 小澤 健太郎 / Kentaro Ozawa (奈良県立医科大学 / Nara Medical University, Japan)
山門 穂高 / Hodaka Yamakado (京都大学大学院医学研究科 臨床神経学  / Department of Neurology, Kyoto University Graduate School of Medicine, Japan)

Parkin mutations impair mitochondrial function and enhance neurodegeneration in synucleinopathy associated with dementia with Lewy bodies

  • O2-I-5-3
  • Jianshe Wei:1 Yi Wang:1 Jiannan Wu:1 Nannan Wei:1 Ping Li:1 Huimin Liang:1 Masayo Fujita:2 Makoto Hashimoto:2 
  • 1:Institute for Brain Science Research 2:Tokyo Metropolitan Institute of Medical Sciences, Japan 

Mutations in parkin, a ubiquitin ligase, cause early-onset familial Parkinson's disease. There are many reports for the functions of parkin, but the precise mechanism of parkin/PARK2 in dementia with Lewy bodies and Parkinson's disease remains unknown. Our purpose was to investigate the cellular features of parkin in synucleionopathies, and the relationships to mitochondrial function and synuclein as well as neurodegeneration associated with demantia with Lewy bodies. We constructed the parkin plasmid in Tet-off system and establish the stable parkin over-expressing cell lines, and observed parkin cellular distribution and function by immunofluorescence. The cell viability and degeneration were analyzed by LDH, WST-1 and TUNEL assays. Synuclein metabolism related to autophagy was probed by immunoblot. The results showed Parkin wild type almost disperses in the cytoplasm, while the mutants take the shape of small granular structure to form the perinuclear inclusions causing mitochondrial dysfunction. Parkin WT regulates synuclein autophagy by mTOR pathway, promotes β-syn P123H into autophagolysosome and further degradation. Disease-causing mutations in Parkin increase the accumulation of β-syn P123H protein and enhance the autophagic cell death associated dementia with Lewy bodies.

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