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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
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)

Impaired autophagic flux is linked to calcium-dependent dopaminergic neuronal death

  • S2-C-1-4
  • Young Jun Oh:1 
  • 1:Yonsei University, Korea 

Autophagy is a conserved process that mediates a removal of dysfunctional organelles and abnormal protein aggregated. Recently, accumulating evidence indicates that dysregulation of autophagy underlies the pathophysiology of several neurodegenerative diseases. Using culture models of Parkinson’s disease, we have investigated whether and how prototypic autophagic events occur upon exposure to N-methyl-4-phenylpyridinium or nigericin that all triggers calcium-dependent neurodegeneration. We have found that these drugs equally induce morphological and biochemical changes typical of autophagy. These include accumulation of autophagic vacuoles, appearance of LC3-II form, and alteration in expression and distribution of p62. Further investigation has indicated that drug-induced autophagic phenomena are largely the consequences of an impaired autophagic flux. In these cell death paradigms, we have intriguingly found that Bak, a prototypic proapoptotic proteins of the Bcl-2 family exerts a protective role via reduction of the area occupied by swollen vacuoles and appearance of LC3-II form whereas silencing of Bak aggravates these phenomena. Further study has indicated that protective role for Bak is primarily ascribed to its regulatory effect on maintenance of autophagic flux and vacuole homeostasis. For a comparison purpose, I’ll provide data showing effect for 6-hydroxydopamine on autophagy.

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