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Parkinson's Disease and Related Disorders

開催日 2014/9/13
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

The downregulation of longevity-related gene, FOXO3 induces the neurodegeneration of the Lewy body disease model cells

  • P3-287
  • 南山 誠 / Makoto Minamiyama:1 龍 訥 / Ne Long :1 能勢-黒川 弓 / Yumi Kurokawa Nose:1 本山 昇 / Noboru Motoyama:1 永井-社本 雅代 / Masayo Shimamoto Nagai:1 茨木 京子 / Kyouko Ibaraki:1 早川 智久 / Tomohisa Hayakawa:1 山田 洋美 / Hiromi Yamada:1 金森 久美子 / Kumiko Kanamori:1 山岡 朗子 / Akiko Yamaoka:2 直井 信 / Makoto Naoi:3 丸山 和佳子 / Wakako Maruyama:1 
  • 1:国立長寿医療研究センター・加齢健康脳科学・病態制御 / National Center for Geriatrics and Gerontology 2:国立長寿医療研究センター・神経内科 / Dept Neurol, Natl Cent for Geriat and Gerontol, Aichi, Japan 3:愛知学院大学・心身科学 / Facul Psychol and Physic Sci, Aichi Gakuin Univ , Aichi, Japan 

Lewy body diseases (LBDs) are the neurodegeneration represented Parkinson disease (PD). These are pathologically characterized by the neuronal inclusion (Lewy Body). Several disease-related genes are discovered from the familial cases, and being studied especially in PD, but the pathogenesis is still unsolved. So far, mainly two types of LBDs model have been developed to understand the LBDs pathogenesis. One is the pharmacological model like rotenone, and another is the genetical model with the α-synuclein (α-syn), the major ingredient of Lewy body. The chemical model was originally found to cause Parkinsonism by neurotoxicity, but they cannot express all LBD pathology. On the other hand, the genetical model with α-syn cannot have the neuronal death. We newly focused on the point that these diseases develop in elderliness, and are progressing with aging. Therefore, we started to create the new LBD model considered aging. FOXO3 is a multifunctional transcription factor, which functions in stress response, apoptosis, tumor suppression, and etc. This gene is also reported to be associated with longevity in humans. On the other hands, FOXO3 is reported to be colocalized in Lewy body of the patients´ autopsied brain, and may have some role for LBD pathology. We analyzed the influence of LBD model cells which were made by α-syn overexpression, with the downregulation of FOXO3 by RNA interferance. FOXO3 downregulated cells were more fragile compared with the control. And the α-syn overexpressed cells upregulated FOXO3, and this gene was suggested to be concerned with stress response. We searched the influence of FOXO3 dysfunction biochemically and pathologically with westernblotting, RT-PCR, and etc, and the autophagy system was found to be impaired in the FOXO3 downregulated cells. We are now studying about the influence for the oxidative stress, and also want to report about the mouse model.

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