Neuro-cell biological studies of alpha-synuclein

• Project/Area Number: 23500408
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neuroscience in general
• Research Institution: 独立行政法人国立精神・神経医療研究センター (2013); Tokyo Metropolitan Institute of Medical Science (2011-2012)
• Principal Investigator: UEDA Kenji 独立行政法人国立精神・神経医療研究センター, 病院・副院長室, 研究生 (90261180)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: シヌクレイン / ミトコンドリア / ATP産生 / チューブリン / 神経突起伸長 / 細胞増殖 / ドーパミン / カルパイン / αシヌクレイン / MAP / 微小管 / 神経変性

Research Abstract

After the biochemical examination of SDS-insoluble materials of the brains with Alzheimer's disease, we identified human alpha-Synuclein by cDNA cloning. Some missense mutations of the gene for alpha-Synuclein were found as causal genes for the patients with familial Parkinson's disease and with familial dementia with Lewy bodies. However, physiological functions of alpha-Synuclein remain elusive. In the present studies, we have shown that alpha-Synuclein is localized in the inner membrane of neuronal mitochondria, and that alpha-Synuclein binds adenylate translocator. It suggests that alpha-Synuclein may regulate the production of ATP through mitochondrial permeability transition pore. Using in vitro cell culture systems, we showed that alpha-Synuclein promotes cell proliferation and affects early neurite outgrowth. It was shown that these effects are through microtubule formation via tubulin assembly by alpha-Synuclein.

Research Products

• [Journal Article] Alpha-Synuclein promotes early neurite outgrowth in primary cultured neurons (2013)
  • Author(s): Liu G, Wang P, Li X, Li Y, Xu S, Ueda K, Chan P, Yu S
  • Journal Title: J Neural Transm. Volume: 120 Issue: 9 Pages: 1331-1343
  • DOI: 10.1007/s00702-013-0999-8
  • Peer Reviewed
• [Journal Article] Nuclear translocation of alpha-synuclein increases susceptibility of MES23.5 cells to oxidative stress (2013)
  • Author(s): Zhou M, Xu S, Mi J, Ueda K, Chan P
  • Journal Title: Brain Res. Volume: 1500 Pages: 19-27
  • DOI: 10.1016/j.brainres.2013.01.024
  • Peer Reviewed
• [Journal Article] Alpha-synuclein promotes early neurite outgrowth in cultured primary neurons (2013)
  • Author(s): Liu G, Wang P, Li X, Li Y, Xu S, Ueda K, Chan P, Yu S
  • Journal Title: J. Neural Transm. Epub ahead of print] PMID: 23443897 Volume: in press
  • Peer Reviewed
• [Journal Article] Demonstration of three dopamine molecules bound to alopha-synuclein: Implication of oligomerization at the initial stage (2012)
  • Author(s): S Shimotakahara, Y Shiroyama, T Fujimoto, M Akai, T Onoue, H Seki, S Kado, T Machinami, Y Shibusawa, K Ueda, M Tashiro
  • Journal Title: J. Biophysical Chem. Volume: 3 Issue: 02 Pages: 149-155
  • DOI: 10.4236/jbpc.2012.32017
  • Peer Reviewed
• [Journal Article] Melatonin reduces the expression of α-synuclein in the dopamine containing neuronal regions of amphetamine-treated postnatal rats (2012)
  • Author(s): Sae-Ung K, Uéda K, Govitrapong P, Phansuwan-Pujito P
  • Journal Title: J. Pineal Res Volume: 52 Issue: 1 Pages: 128-137
  • DOI: 10.1111/j.1600-079x.2011.00927.x
  • Peer Reviewed
• [Journal Article] α-Synuclein promotes clathrin-mediated NMDA receptor endocytosis and attenuates NMDA-induced dopaminergic cell death (2011)
  • Author(s): Cheng F, Li X, Li Y, Wang C, Wang T, Liu G, Baskys A, Uéda K, Chan P, Yu S
  • Journal Title: J. Neurochem Volume: 119 Issue: 4 Pages: 815-825
  • DOI: 10.1111/j.1471-4159.2011.07460.x
  • Peer Reviewed
• [Journal Article] α-Synuclein functions as a negative regulator for expression of tyrosine hydroxylase (2011)
  • Author(s): Li YH, Gao N, Ye YW, Li X, Yu S, Yang H, Uéda K, Chan P
  • Journal Title: Acta Neurol. Belg Volume: 111 Pages: 130-135
  • URL: http://www.actaneurologica.be/acta/article.asp?lang=en&navid=137&id=15088&mod=acta
  • Peer Reviewed
• [Journal Article] Increased expression of α-synuclein in aged human brain associated with neuromelanin accumulation (2011)
  • Author(s): Xuan Q, Xu SL, Lu DH, Yu S, Zhou M, Uéda K, Cui YQ, Zhang BY, Chan P
  • Journal Title: J. Neural Transm Volume: 118 Issue: 11 Pages: 1575-1583
  • DOI: 10.1007/s00702-011-0636-3
  • Peer Reviewed
• [Journal Article] C-terminal part of α-synuclein mediates its activity in promoting proliferation of dopaminergic cells (2011)
  • Author(s): Yin J, Han J, Zhang C, Ma QL, Li X, Cheng F, Liu G, Li Y, Uéda K, Chan P, Yu S
  • Journal Title: J. Neural Transm Volume: 118 Issue: 8 Pages: 1155-1164
  • DOI: 10.1007/s00702-011-0592-y
  • Peer Reviewed
• [Journal Article] α-Synuclein overexpression impairs mitochondrial function by associating with adenylate translocator (2011)
  • Author(s): Zhu Y, Duan C, Lü L, Gao H, Zhao C, Yu S, Uéda K, Chan P, Yang H
  • Journal Title: Int. J. Biochem. Cell Biol Volume: 43 Issue: 5 Pages: 732-741
  • DOI: 10.1016/j.biocel.2011.01.014
  • Peer Reviewed
• [Journal Article] α-Synuclein functions as a negative regulator for expression of tyrosine hydroxylase (2011)
  • Author(s): Li YH, Gao N, Ye YW, Li X, Yu S, Yang H, Ueda K, Chan P
  • Journal Title: Acta Neurol. Belg. Volume: 111 Pages: 130-135
  • Peer Reviewed
• [Journal Article] Increase expression of α-synuclein in aged human brain associated with neuromelanin accumulation. (2011)
  • Author(s): Xuan Q, Xu SL, Lu DH, Yu S, Zhou M, Ueda K, Cui YQ, Zhang BY, Chan P
  • Journal Title: J. Neural Transm. Volume: 118 Pages: 1575-1583
  • Peer Reviewed
• [Journal Article] C-terminal part of α-synuclein mediates its activity in promoting proliferation of dopaminergic cells. (2011)
  • Author(s): Yin J, Han J, Zhang C, Ma QL, Li X, Cheng F, Liu G, Li Y, Ueda K, Chan P, Yu S
  • Journal Title: J. Neural Transm. Volume: 118 Pages: 1155-1164
  • Peer Reviewed
• [Presentation] Protective effect of melatonin on the expression of α-synuclein in hippocampus of amphetamine-treated postnatal rat (2012)
  • Author(s): Leeboonngam T, Sae-Ung K, Uéda K, Govitrapong P, Phansuwan-Pujito P
  • Organizer: The 11th BiennialMeeting of the Asian-Pacific Society for Neurochemistry, APSN 2012
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2012-10-01
• [Presentation] C-Terminal part of α-synuclein mediates its activity in promoting proliferation of dopaminergic cells (2011)
  • Author(s): Yin J, Wang T, Han J, Zhang C, Ma Q, Li X, Cheng F, Liu G, Li Y, Uéda K, Chan P, Yu S
  • Organizer: 2011 International Conference on Molecular Neurodegeneration
  • Place of Presentation: Shanghai, China
  • Year and Date: 2011-09-22
• [Presentation] Protective effect of melatonin on the dopamine pathway from amphetamine-induced neurotoxicity in postnatal rats (2011)
  • Author(s): Sae-Ung K, Govitrapong P, Uéda K, Phansuwan-Pujito P
  • Organizer: The 23rd BiennialMeeting of the International Society for Neurochemistry, ISN
  • Place of Presentation: Athens, Greece
  • Year and Date: 2011-08-31
• [Presentation] Protective effect of melatonin on the dopamine pathway from amphetamine-induced neurotoxicity in postnatal rats (2011)
  • Author(s): Sae-Ung K, Govitrapong P, Ueda K, Phansuwan-Pujito P
  • Organizer: The 23rd Biennial Meeting of the International Society for Neurochemistry (ISN)
  • Place of Presentation: Athens, Greece
• [Remarks] ホームページ
  • URL: http://www.ncnp.go.jp/hospital/