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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)

Spreading of pathological alpha-synuclein explain the disease progression

  • S2-C-1-6
  • 長谷川 成人 / Masato Hasegawa:1 
  • 1:東京都医学総合研究所 / Tokyo Metropolitan Institute of Medical Science, Japan 

Progressive accumulation of alpha-synuclein (aS) and neurodegeneration are the defining neuropathological feature of Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). We established a novel method for introducing fibrils made of aS or tau into cultured cells using lipofection reagents, and proposed a hypothesis that intracellular abnormal proteins propagate from cell to cell and this spreading can explain the disease progression. We demonstrated that inoculation of synthetic aS fibrils efficiently induced hyperphosphorylated aS pathology in wild-type mice. Mice injected with aS fibrils developed abundant Lewy body / Lewy neurite-like pathology. Immunoblot analysis clearly showed that endogenous mouse aS started to accumulate 1 ~ 3 months after inoculation, while injected human aS fibrils degraded in a week. Furthermore, inoculations of Sarkosyl-insoluble aS from DLB patients induced similar aS pathology. Interestingly, abnormal aS pathology was restricted mainly to substantia nigra, amygdala, and stria terminalis at one month after injection, when fibrils were injected into substantia nigra. However, when fibrils were injected into striatum, the pathology was widely distributed bilaterally throughout the brain, showing that propagation of pathological aS occurred along neural circuits and involved trans-synaptic transport. In addition, inoculation of insoluble aS accumulated in wild-type mice into other wild-type mice also induced aS pathology, indicating that aS fibrils show prion-like

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