演題詳細
Symposium
日本-韓国神経科学学会合同シンポジウム:Molecular Mechanisms underlying Parkinson Disease
Joint Symposium of the Japan Neuroscience Society and the Korean Society of Brain and Neuroscience:Molecular Mechanisms underlying Parkinson Disease
開催日 | 2014/9/12 |
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時間 | 9:00 - 11:00 |
会場 | Room C(502) |
Chairperson(s) | 望月 秀樹 / Hideki Mochizuki (大阪大学医学系研究科神経内科学 / Department of Neurology, Osaka University Graduate School of Medicine, Japan) Young Jun Oh (Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Korea) |
Lysosomal dysfunction is the key factor for propagation of synucleinopathy
- S2-C-1-2
- Seung-Jae Lee:1 Eun-Jin Bae:1 Na-Young Yang:1 Cheol-Soon Lee:1 He-Jin Lee:1 Eliezer Masliah:2 Pablo Sardi:3
- 1:Konkuk University, Seoul, Korea 2:University of California, San Diego, La Jolla, CA, USA 3:Genzyme, a Sanofi Company, Framingham, MA, USA
Deposition of &alpha-synuclein aggregates occurs widely in the central and peripheral nervous systems in Parkinson's disease (PD). Although recent evidence has suggested that cell-to-cell transmission of &alpha-synuclein aggregates drives the progression of PD, the mechanism by which &alpha-synuclein aggregates spread remains undefined. Here, we show that &alpha-synuclein aggregates are perpetually transmitted through a continuous cycle involving uptake of external aggregates, co-aggregation with endogenous &alpha-synuclein, and exocytosis of the co-aggregates. Moreover, we found that glucocerebrosidase 1 depletion, which has previously been strongly associated with PD and increased cognitive impairment, promoted propagation of &alpha-synuclein aggregates. Depletion of other genes such as ctsd (cathepsin D) and ATP13A2, resulted in mixed outcomes in lysosomal functions. The cell lines with these gene depletions further confirmed that lysosomal dysfunction is the key modulator of spreading of synucleinopathy. These studies define how &alpha-synuclein aggregates spread among neuronal cells and explain how lysosomal dysfunction increase the risk of developing PD and other synucleinopathies.