Neuronal differentiation of stem cells by beta-synuclein

• Project/Area Number: 19700332
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Tokyo Metropolitan Organization for Medical Research
• Principal Investigator: FUJITA Masayo Tokyo Metropolitan Organization for Medical Research, 東京都神経科学総合研究所, 主任研究員 (90415539)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥2,890,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥1,200,000 (Direct Cost: ¥1,200,000)
• Keywords: 神経変性疾患 / シヌクレイン / 分化 / トランスジェニックマウス / レビー小体型認知症 / シヌクレイノパチー / 細胞分化 / 神経変性

Research Abstract

シヌクレイン(syn)は神経組織に多く発現する生理機能未知のタンパクで、α、β、yの3種が存在する。本研究では、βsynに着目し、生理機能および病態発症への関与を検討した。 Βsyn過剰発現細胞は、cAMPの活性化を通し、神経分化誘導作用を持つ可能性が推察された。またβsynの変異型をマウスに過剰発現させると、神経軸索末端の異常および記憶や運動の障害を引き起こし、新しい神経変性疾患のモデルとなると考えられた。

Research Products

• [Journal Article] Protective role of endogenous gangliosides for lysosomal pathology in a cellular model of synucleinopathies (2009)
  • Author(s): Wei J, Fu.iita M, Nakai M, Waragai M, Sekigawa A, Sugama s, Takenouchi T, Masliah E, Hashimoto M
  • Journal Title: Am. J. Pathol 175 Pages: 1891-1909
  • Peer Reviewed
• [Journal Article] Microglial activation is inhibited by corticosterone in dopaminergic neurodegeneration J (2009)
  • Author(s): Sugama S Takenouchi T, Kitani H, Fu.iita M, Hashimoto M
  • Journal Title: Neuroinmunol 208 Pages: 104-114
  • Peer Reviewed
• [Journal Article] The Activation of P2χ7 Receptor Impairs Lysosomal Functions and Stimulates the Release of Autophagolysosomes in Microglial (2009)
  • Author(s): Takenouchi T, Nakai M, Iwamaru Y, Sugama S, Tsukimoto, M, Fu.jita M, Wei J, Sekigawa A, Sato M, Kojima, S, Kitani H, Hashimoto M
  • Journal Title: Cells J Immunol 182 Pages: 2051-2062
  • Peer Reviewed
• [Journal Article] Differential microglia and neuronal activation between acute stress and lipopolysaccharide treatment J (2009)
  • Author(s): Sugama, S Takenouchi T, Fu.iita M, Conti, B Hashimoto M.
  • Journal Title: Neuroiimnunol 207 Pages: 24-31
  • Peer Reviewed
• [Journal Article] Differential microglial activation between acute stress and lipopolysaccharide treatment (2009)
  • Author(s): Sugama, S Takenouchi T, Fujita M, Conti B, Hashimoto M
  • Journal Title: J Neuroimmunol. 207 Pages: 24-31
  • Peer Reviewed
• [Journal Article] The Activation of P2X7 Receptor Impairs Lysosomal Functions and Stimulates the Release of Autophagolysosomes in Microglial Cells. (2009)
  • Author(s): Takenouchi T, Nakai M, Iwamaru Y, Sugama S, Tsukimoto, M, Fujita M. Wei J, Sekigawa A, Sato M, Kojima, S, Kitani H, Hashimoto M.
  • Journal Title: J Immunol. 182 Pages: 2051-2062
  • Peer Reviewed
• [Journal Article] Microglial activation is inhibited by corticosterone in dopaminergic neurodegeneration (2009)
  • Author(s): Sugama, S Takenouchi T, Kitani H, Fuiita. M, Hashimoto M
  • Journal Title: J Neuroimmunol. 208 Pages: 104-114
  • Peer Reviewed
• [Journal Article] Ghafourifar p. Mitochondria association of alpha-synuclein causes oχi dative stress (2008)
  • Author(s): Parihar MS, Parihar A, Fu.iita M Hashimoto M
  • Journal Title: Cell Mol Life Sci 65 Pages: 1272-84
  • Peer Reviewed
• [Journal Article] シヌクレイノパチー (2008)
  • Author(s): 藤田雅代,橋本款
  • Journal Title: モダンフィジシヤン 28 Pages: 1808-1811
• [Journal Article] βシヌクレインの変異による神経変性促進の可能性 (2008)
  • Author(s): 藤田雅代,橋本款
  • Journal Title: 医学のあゆみ 224 Pages: 303-304
• [Journal Article] Mitochondrial association of alnha-svnuclein causes oxidative stress. (2008)
  • Author(s): Parihar MS, Parihar A, Fuiita M. Hashimoto M, Ghafourifar P
  • Journal Title: Cell Mol Life Sci 65 Pages: 1272-1284
  • Peer Reviewed
• [Journal Article] Activin as ananti-inflanmatory cytokine produced by microglia (2007)
  • Author(s): Sugama, S., Takenouchi, T., Kitani, H. Fu.iita. M., Hashimoto, M
  • Journal Title: J Neuroimmunol 192(1-2) Pages: 31-39
  • Peer Reviewed
• [Journal Article] Plasma levels of DJ-1 as a possible marker for progression of sporadic Parkinson' s disease lewy bodies (2007)
  • Author(s): Waragai, M., Nakai, M. ,Wei,J., Fu.iita M. . Mizuno, H., Ho, G., Masliah, E., Akatsu H., Yokochi, .Hashimoto, M
  • Journal Title: Neurosci Lett 425(1) Pages: 18-22
  • Peer Reviewed
• [Journal Article] Enhanced lysosomal pathology caused by beta-synuclein mutants linked to dementia with (2007)
  • Author(s): Wei, J., Fu.iita. M. Nakai, M,Waragai, M., Watabe, K., Akatsu, H., Rockenstein, E Masliah, E. , Hashimoto, M
  • Journal Title: J Biol Chem 282 Pages: 28904-28914
  • Peer Reviewed
• [Journal Article] Stress induced morphological microglial activation in the rodent brain Involvement of interleukin-18 (2007)
  • Author(s): Sugama, S., Fu.jita. M.. Hashimoto, M. Conti, B
  • Journal Title: Neuroscience 146 Pages: 1388-1399
  • Peer Reviewed
• [Journal Article] Eχpression of alpha-synuclein, apresynaptic protein implicated in Parkinson' s disease in erythropoietic lineage line (2007)
  • Author(s): Nakai, M. Fu.iita. M. Waragai, M Sugama, s. Wei, J Akatsu, H. Ohtaka-Maruyama, C., Okado, H., Hashimoto M
  • Journal Title: Biochem Biophys Res Conmun 358 Pages: 104-110
  • Peer Reviewed
• [Journal Article] Prion infection correlates with hypersensitivity of P2×7 nucleotide receptor in a mouse microglial cell (2007)
  • Author(s): Takenouchi, T., Iwamaru, Y., Imamura, M., Kato, N., Sugama, s., Fu.iita. M., Hashimoto, M., Sato, M., Okada, H., Yokoyama, T., Mohri, S., Kitani, H.
  • Journal Title: FEBS Lett 581 Pages: 3019-3026
  • Peer Reviewed
• [Journal Article] alpha-Synuclein Stimulates Differentiation of Osteosarcoma (2007)
  • Author(s): Fu.iita. M., Sugama, S., Nakai, M., Takenouchi, T., Wei, J, Urano, T., Inoue s., Hashimoto, M
  • Journal Title: Cells RELEVANCE TO DOWN-REGULATION OF PROTEASOME ACTIVITY. J Biol Chem 282 Pages: 5736-5748
  • Peer Reviewed
• [Journal Article] Enhanced lysosomal pathology caused by beta -synuclein mutants linked to dementia with lewy bidies (2007)
  • Author(s): Wei, J
  • Journal Title: J Biol Chem 282 Pages: 28904-28914
  • Peer Reviewed
• [Journal Article] Expression of alpha -synuclein, a presynaptic protein implicated in Parkinson's disease,in erythropoietic lineage (2007)
  • Author(s): Nakai, M
  • Journal Title: Biochem Biophys Res Commun 358 Pages: 104-110
  • Peer Reviewed
• [Journal Article] Stress induced morphological microglial activation in the rodent brain:Involvement of interleukin-18 (2007)
  • Author(s): Sugama, S
  • Journal Title: Neuroscience 146 Pages: 1388-1399
  • Peer Reviewed
• [Journal Article] Prion infection correlates with hypersensitivity of P2X7 nucleotide receptor in amouse microglial cell line (2007)
  • Author(s): Waragai, M
  • Journal Title: Neurosci Left 581 Pages: 3019-3026
  • Peer Reviewed
• [Journal Article] Plasma levels of DJ-1 as a possible marker for progression of sporadic Parkinson's disease (2007)
  • Author(s): Sugama, S
  • Journal Title: J Neuroimmunol 425 Pages: 18-22
  • Peer Reviewed
• [Presentation] βシヌクレイン(P123H)過剰発現型新規トランスジェニックマウスの解析 (2008)
  • Author(s): 藤田雅代、関川明生、魏建設、藁谷正明、津久井通、井上聡、橋本款
  • Organizer: 第31回日本分子生物学会年会・第81回日本生化学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] βシヌクレイン(P123H)過剰発現型トランスジェニックマウスの解析 (2008)
  • Author(s): 藤田雅代、関川明生、魏建設、藁谷正明、津久井通、井上聡、橋本款
  • Organizer: BMB2008
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] A novel mouse model of Lewy body disease (2008)
  • Author(s): Hashimoto M, Fuiita M. Nakai, M, Sekigawa A
  • Organizer: 第17回パーキンソン病治療学会
  • Place of Presentation: 東京(ノバルティスファーマ主催)
  • Year and Date: 2008-09-27
• [Presentation] Protectiverole of glycoshingolipids for lysosoma pathology in synucleinopathies (2008)
  • Author(s): Wei J, Nakai M._Fujita M. Hashimoto M
  • Organizer: Neuro2008(第31回日本神経科学大会)
  • Place of Presentation: 東京
  • Year and Date: 2008-07-10
• [Presentation] Protectiverole of glycoshingolipids for lysosomal pathology in synucleinopathies. (2008)
  • Author(s): Wei J, Nakai M, Fuiita M, Hashimoto M.
  • Organizer: 第31回日本神経科学大会
  • Place of Presentation: 東京
  • Year and Date: 2008-07-10
• [Presentation] βシヌクレイン(P123H)過剰発現型トランスジェニックマウスの解析 (2008)
  • Author(s): 藤田雅代、中井雅晶、魏建設、藁谷正明、津久井通、井上聡、橋本款
  • Organizer: 第49回日本神経病理学会
  • Place of Presentation: 東京
  • Year and Date: 2008-05-20
• [Presentation] Enhanced lysosomal pathology caused by beta-synuclein mutants linked to dementia with Lewy bodies (2007)
  • Author(s): Wei, J., Fuiita, M. ,Nakai, M, Hashimoto,M.
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] シヌクレイノパチーと癌に対するシヌクレイン蛋白の多彩な病理的作用 (2007)
  • Author(s): 藤田雅代、魏建設、中井雅晶、藁谷正明、橋本款
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11
• [Presentation] シヌクレイノパチ」と癌に対するシヌクレイン蛋白の多彩な病理的作用 (2007)
  • Author(s): 藤田 雅代
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11
• [Presentation] Enhanced lysosomal pathology caused by beta-synuclein mutants linked to dementia with Lewy bodies (2007)
  • Author(s): Wei, J
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11
• [Presentation] Ho, G., Rockenstein, E., Masliah, E. Enhanced lysosomal pathology caused by beta-synuclein mutants linked to dementia with Lewy body (2007)
  • Author(s): Hashimoto, M., Wei, J., Fujita. M。Nakai, M
  • Organizer: Annual meeting of Society for Neuroscience
  • Place of Presentation: San Diego
  • Year and Date: 2007-11-05
• [Presentation] Enhanced lysosomal pathology caused by beta-synuclein mutants linked to dementia with Lewy body. (2007)
  • Author(s): Hashimoto, M
  • Organizer: Annual meeting of Societyfor Neuroscience
  • Place of Presentation: San Diego
  • Year and Date: 2007-11-05
• [Presentation] 変異型βシヌクレインによる神経変性機序の解析 (2007)
  • Author(s): 橋本款、魏建設、中井雅晶、藤田雅代
  • Organizer: Neuro2007(第30回日本神経科学大会第50回日本神経化学大会第17回日本神経回路学会大会合同大会)
  • Place of Presentation: 横浜
  • Year and Date: 2007-09-11
• [Presentation] βシヌクレイン(P123H)過剰発現型トランスジェニックマウスの解析 (2007)
  • Author(s): 橋本 款
  • Organizer: 第30回日本神経科学大会第50回日本神経化学大会第17回日本神経回路学会大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-09-11
• [Presentation] βシヌクレイン(P123H)過剰発現型トランスジェニックマウスの解析 (2007)
  • Author(s): 藤田雅代、中井雅晶、魏建設、藁谷正明、津久井通、井上聡、橋本款
  • Organizer: 第48回日本神経病理学会
  • Place of Presentation: 東京
  • Year and Date: 2007-05-30
• [Presentation] 赤芽球および赤血球におけるαシヌクレインの発現 (2007)
  • Author(s): 中井雅晶、藁谷正明、藤田雅代、魏建設、洲鎌秀永、赤津裕康、丸山千秋、岡戸晴生、橋本款
  • Organizer: 第143回目本獣医学会
  • Place of Presentation: 茨城県つくば市
  • Year and Date: 2007-04-03
• [Presentation] 赤芽球および赤血球におけるαシヌクレインの発現 (2007)
  • Author(s): 中井 雅晶
  • Organizer: 第143回日本獣医学会
  • Place of Presentation: 茨城県つくば市
  • Year and Date: 2007-04-03
• [Presentation] ヒト変異型βシヌクレイン(P123H β-syn)発現トランスジェニックマウスにおけるphenotypeの解析 (2007)
  • Author(s): 中井雅晶、藤田雅代、魏建設、藁谷正明、井上聡、津久井通、橋本款
  • Organizer: 第144回目本獣医学会
  • Place of Presentation: 麻生大学(神奈川)
  • Year and Date: 2007-03-30