Study of food components to suppress the progress of Parkinson's disease: from the metabolism of dopamine

• Project/Area Number: 18K11004
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Fujita Health University
• Principal Investigator: Nakashima Akira 藤田医科大学, 医学部, 教授 (20180276)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: パーキンソン病、 / ドパール（DOPAL） / キサンチン誘導体 / ドーパミン代謝 / NT5DC2 / パーキンソン病 / DOPAL / 食品成分

Outline of Final Research Achievements

In Parkinson's disease, dopaminergic neurons in the substantia nigra of the midbrain are selectively impaired, and the one reason is assumed to be excessive accumulation of dopamine (DA) metabolite, 3,4-Dihydroxyphenylacetaldehyde (DOPAL) , in the cells. In this study, we found that not only xanthine derivatives such as caffeine but also certain flavonoids in food components have an extremely strong effect to suppress the production of DOPAL. We also discovered that the intracellular protein NT5DC2 may affect DA synthesis through the regulation of tyrosine hydroxylase activity.

Academic Significance and Societal Importance of the Research Achievements

食品成分とパーキンソン病発症の関係については、コーヒーに含まれるカフェインが発症リスクを抑えることが疫学調査から報告されているが、メカニズムについては明確にされているわけではない。本研究はミトコンドリア障害を誘発するドーパミン代謝産物ドパールの神経細胞内への過剰蓄積と、それを抑制することができる食品成分の解析を行い、ドーパミンの合成・代謝の視点から細胞障害メカニズムの解明を目指したものである。中脳黒質のドーパミン神経細胞の選択的な障害はパーキンソン病の特徴である。日常摂取する食品成分によるドパールの細胞内蓄積を抑制するメカニズムを明確にすることができれば、パーキンソン病発症の予防に有益となる。

Research Products

• [Journal Article] NT5DC2 affects the phosphorylation of tyrosine hydroxylase regulating its catalytic activity. (2020)
  • Author(s): Nakashima A, Yamaguchi H, Kondo M, Furumura T, Kodani Y, Kaneko YS, Kawata M, Nagasaki H, Ngatsu T, Ota A
  • Journal Title: Journal of Neural Transmission Volume: 127 Issue: 12 Pages: 1631-1340
  • DOI: 10.1007/s00702-020-02236-5
  • Peer Reviewed / Open Access
• [Journal Article] Monoamine Oxidase Inhibitor (MAO-I)-Mediated Neuroprotection for Treating Parkinson’s Disease (2020)
  • Author(s): Nagatsu T,Nakashima A
  • Journal Title: NeuroPsychopharmacotherapy Volume: 3 Pages: 1-21
  • DOI: 10.1007/978-3-319-56015-1_238-1
  • ISBN: 9783319560151
  • Peer Reviewed
• [Journal Article] Identification by nano-LC-MS/MS of NT5DC2 as a protein binding to tyrosine hydroxylase: Down-regulation of NT5DC2 by siRNA increases catecholamine synthesis in PC12D cells. (2019)
  • Author(s): Nakashima A, Yamaguchi H, Kodani Y, Kaneko YS, Kawata M, Nagasaki H, Nagatsu T, Ota A.
  • Journal Title: Biochem Biophys Res Commun. Volume: 516(4) Issue: 4 Pages: 1060-1065
  • DOI: 10.1016/j.bbrc.2019.06.156
  • Peer Reviewed / Open Access
• [Journal Article] Human tyrosine hydroxylase in Parkinson's disease and in related disorders. (2019)
  • Author(s): Nagatsu T, Nakashima A, Ichinose H, Kobayashi K.
  • Journal Title: J Neural Transm (Vienna) Volume: 126(4) Issue: 4 Pages: 397-409
  • DOI: 10.1007/s00702-018-1903-3
  • Peer Reviewed