Association of between oxidative modification of alpha-synuclein under dopamine metabolism and intracellular stability or propagation

• Project/Area Number: 15K09315
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Tottori University
• Principal Investigator: NAKASO Kazuhiro 鳥取大学, 医学部, 准教授 (30379648)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: パーキンソン病 / synuclein / 細胞間伝播 / 酸化修飾 / シヌクレイン / カテコールアミン / オートファジー

Outline of Final Research Achievements

The association between oxidative modification of α-synuclein under dopamine metabolism and intracellular stability or propagation of α-synuclein was investigated. α-Synuclein was oxidatively modified at 127th methionine residue under dopamine existing condition and was controlled its stability by autophagy/lysosome system. Secretion of α-synuclein was dependent not only on exosome release but also on non-exosomal release. Secretion of α-synuclein was enhanced under dopamine metabolism. In order to detect oxidative modification of α-synuclein at 127th methionine residue, specific antibody against α-synuclein including methionine sulfoxide was raised. Using this antibody oxidative modification of α-synuclein was successfully detected.

Research Products

• [Journal Article] α-Tocopherol promotes HaCaT keratinocyte wound repair through the regulation of polarity proteins leading to the polarized cell migration. (2018)
  • Author(s): Horikoshi Y, Kamizaki K, Hanaki T, Morimoto M, Kitagawa Y, Nakaso K, Kusumoto C, Matsura T.
  • Journal Title: Biofactors Volume: 44 Issue: 2 Pages: 180-191
  • DOI: 10.1002/biof.1414
  • Peer Reviewed / Open Access
• [Journal Article] Rice Bran Dietary Supplementation Improves Neurological Symptoms and Loss of Purkinje Cells in Vitamin E-Deficient Mice. (2016)
  • Author(s): Takahashi T, et al.
  • Journal Title: Yonago Acta Medica Volume: 59 Pages: 188-195
  • Peer Reviewed / Open Access
• [Journal Article] Preconditioning by Low Dose LPS Prevents Subsequent LPS-Induced Severe Liver Injury via Nrf2 Activation in Mice. (2016)
  • Author(s): Nakasone M, et al.
  • Journal Title: Yonago Acta Medica Volume: 59 Pages: 223-231
  • NAID: 120005842977
  • Peer Reviewed / Open Access
• [Journal Article] Nicotine enhances the malignant potential of human pancreatic cancer cells via activation of atypical protein kinase C. (2016)
  • Author(s): Hanaki T, Horikoshi Y, Nakaso K, Nakasone M, Kitagawa Y, Amisaki M, Arai Y, Tokuyasu N, Sakamoto T, Honjo S, Saito H, Ikeguchi M, Yamashita K, Ohno S and Matsura T
  • Journal Title: Biochim Biophys Acta Volume: 1860 Issue: 11 Pages: 2404-2415
  • DOI: 10.1016/j.bbagen.2016.07.008
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Allele-specific regulation of mutant Huntingtin by Wig1, a downstream target of p53. (2016)
  • Author(s): Kim SH, et al.
  • Journal Title: Hum Mol Genet. Volume: 25 Pages: 2514-2524
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Estrogen receptor-mediated effect of δ-tocotrienol prevents neurotoxicity and motor deficit in the MPTP mouse model of Parkinson's disease. (2016)
  • Author(s): Nakaso , et al.
  • Journal Title: Neurosci Lett Volume: 610 Pages: 117-122
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Allele-specific regulation of mutant Huntingtin by Wig1, a downstream target of p53 (2016)
  • Author(s): Shahani N, et al.
  • Journal Title: Hum Mol Genet Volume: 印刷中
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] パーキンソン病関連分子α-synucleinの酸化修飾は細胞脆弱性と細胞間の病原タンパク質伝播に関係している (2017)
  • Author(s): 中曽一裕，ほか
  • Organizer: 第70回日本酸化ストレス学会学術集会
• [Presentation] Dopamine-mediated oxidation of methionine 127 in α-synuclein causes cytotoxicity and accumulation of α-synuclein. (2017)
  • Author(s): Nakaso-K, et al.,
  • Organizer: XXIII World Congress of Neurology 2017
  • Int'l Joint Research
• [Presentation] Oxidative modification of α-synuclein by dopamine induces cellular vulnerability and secretion of α-synuclein. (2017)
  • Author(s): Nakaso-K, et al.,
  • Organizer: Society for Neuroscience 2017 Annual Meeting
  • Int'l Joint Research
• [Presentation] 抗酸化能だけではないビタミンEの効果 ～トコトリエノールのシグナル伝達を介した細胞保護機序～ (2017)
  • Author(s): 中曽一裕，松浦達也
  • Organizer: 2017年度生命科学系学会合同年次大会（ConBio2017）
  • Invited
• [Presentation] パーキンソン病モデル細胞・動物に対するビタミンE同族体δトコトリエノールの効果 (2016)
  • Author(s): 中曽一裕 ほか
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2016-09-25
• [Presentation] 米糠成分による神経系保護効果およびマウス運動機能・短気記憶への効果 (2016)
  • Author(s): 髙橋徹，中曽一裕 ほか
  • Organizer: 第27回ビタミンE研究会
  • Place of Presentation: 高松市あなぶきホール（ 高松市）
  • Year and Date: 2016-01-08
• [Presentation] Oxidative modification of alpha-synuclein and protective factor methionine sulfoxide reductase in molecular pathogenesis of Parkinson's disease (2015)
  • Author(s): 中曽一裕 ほか
  • Organizer: BMB2015
  • Place of Presentation: 神戸国際会議場（ 神戸市）
  • Year and Date: 2015-12-01
• [Presentation] Dopamine-mediated oxidation of methionine 127 in alpha-synuclein. (2015)
  • Author(s): 中曽一裕 ほか
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 新潟コンベンションセンター（ 新潟市）
  • Year and Date: 2015-05-20