Identification of Parkinson's disease progression markers based on skeletal muscle-brain axis

• Project/Area Number: 18H02744
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Juntendo University
• Principal Investigator: Saiki Shinji 順天堂大学, 医学部, 先任准教授 (00339996)
• Co-Investigator(Kenkyū-buntansha): 笹澤 有紀子 順天堂大学, 大学院医学研究科, 特任助教 (20594922) ; 天羽 拓 防衛大学校(総合教育学群、人文社会科学群、応用科学群、電気情報学群及びシステム工学群), 応用科学群, 准教授 (40453922) ; 井本 正哉 順天堂大学, 大学院医学研究科, 特任教授 (60213253) ; 赤松 和土 順天堂大学, 大学院医学研究科, 教授 (60338184) ; 石川 景一 順天堂大学, 大学院医学研究科, 准教授 (90733973)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2021: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2020: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
• Keywords: パーキンソン病 / メタボローム解析 / 代謝産物 / 脂肪酸β酸化 / カフェイン代謝 / ポリアミン代謝 / ポリアミン / オートファジー / miRNA / 遠隔効果 / 骨格筋 / 甲状腺 / 肝臓 / 臓器円環 / 神経内科学 / 脂肪酸代謝 / 臓器連関

Outline of Final Research Achievements

Based on the plasma metabolome analysis of Parkinson's disease patients, we have already identified fatty-acid beta-oxidation insufficiency in 2017. Additional metabolome analysis with de novo PD patients showed insufficient beta-oxidation consistent with the previous study, suggesting of the influence of levodopa medication on the metabolic changes.Likewise, metabolic changes in polyamine, which correlated with axonal changes detected by cranial MRI, were identified in this study.

Academic Significance and Societal Importance of the Research Achievements

本研究により、パーキンソン病患者血液を用いた確定診断（カフェイン代謝変化、早期症例における脂肪酸β酸化機能低下）、病状把握（ポリアミン代謝変化）、薬剤の影響（levodopa代謝産物）を判断することが出来るため、侵襲の低いバイオマーカー研究に道を拓いた点に意義があると考える。

Research Products

• [Journal Article] Non-invasive diagnostic tool for Parkinson’s disease by sebum RNA profile with machine learning (2021)
  • Author(s): Uehara Yuya、Ueno Shin-Ichi、Amano-Takeshige Haruka、Suzuki Shuji、Imamichi Yoko、Fujimaki Motoki、Ota Noriyasu、Murase Takatoshi、Inoue Takayoshi、Saiki Shinji、Hattori Nobutaka
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 18550-18550
  • DOI: 10.1038/s41598-021-98423-9
  • Peer Reviewed / Open Access
• [Journal Article] Metabolomic analysis data of MPP+-exposed SH-SY5Y cells using CE-TOFMS (2021)
  • Author(s): Amo Taku、Oji Yutaka、Saiki Shinji、Hattori Nobutaka
  • Journal Title: Data in Brief Volume: 34 Pages: 106707-106707
  • DOI: 10.1016/j.dib.2020.106707
  • Peer Reviewed / Open Access
• [Journal Article] Shared Metabolic Profile of Caffeine in Parkinsonian Disorders (2020)
  • Author(s): Takeshige‐Amano Haruka、Saiki Shinji、Fujimaki Motoki、Ueno Shin‐Ichi、Li Yuanzhe、Hatano Taku、Ishikawa Kei‐Ichi、Oji Yutaka、Mori Akio、Okuzumi Ayami、Tsunemi Taiji、Daida Kensuke、Ishiguro Yuta、Imamichi Yoko、Nanmo Hisayoshi、Nojiri Shuko、Funayama Manabu、Hattori Nobutaka
  • Journal Title: Movement Disorders Volume: 35 Issue: 8 Pages: 1438-1447
  • DOI: 10.1002/mds.28068
  • Peer Reviewed / Open Access
• [Journal Article] A metabolic profile of polyamines in parkinson disease: A promising biomarker (2019)
  • Author(s): Saiki Shinji、Sasazawa Yukiko、Fujimaki Motoki、Kamagata Koji、Kaga Naoko、Taka Hikari、Li Yuanzhe、Souma Sanae、Hatano Taku、Imamichi Yoko、Furuya Norihiko、Mori Akio、Oji Yutaka、Ueno Shin‐Ichi、Nojiri Shuko、Miura Yoshiki、Ueno Takashi、Funayama Manabu、Aoki Shigeki、Hattori Nobutaka
  • Journal Title: Annals of Neurology Volume: 86 Issue: 2 Pages: 251-263
  • DOI: 10.1002/ana.25516
  • Peer Reviewed / Open Access
• [Journal Article] Plasma metabolite biomarkers for multiple system atrophy and progressive supranuclear palsy (2019)
  • Author(s): Mori Akio、Ishikawa Kei-Ichi、Saiki Shinji、Hatano Taku、Oji Yutaka、Okuzumi Ayami、Fujimaki Motoki、Koinuma Takahiro、Ueno Shin-Ichi、Imamichi Yoko、Hattori Nobutaka
  • Journal Title: PLOS ONE Volume: 14 Issue: 9 Pages: e0223113-e0223113
  • DOI: 10.1371/journal.pone.0223113
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Metabolomic analysis revealed mitochondrial dysfunction and aberrant choline metabolism in MPP+-exposed SH-SY5Y cells (2019)
  • Author(s): Amo Taku、Oji Yutaka、Saiki Shinji、Hattori Nobutaka
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 519 Issue: 3 Pages: 540-546
  • DOI: 10.1016/j.bbrc.2019.09.031
  • Peer Reviewed
• [Journal Article] Neuroprotective effects of memantine via enhancement of autophagy (2019)
  • Author(s): Hirano Kazuoki、Fujimaki Motoki、Sasazawa Yukiko、Yamaguchi Akihiro、Ishikawa Kei-Ichi、Miyamoto Kengo、Souma Sanae、Furuya Norihiko、Imamichi Yoko、Yamada Daisuke、Saya Hideyuki、Akamatsu Wado、Saiki Shinji、Hattori Nobutaka
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 518 Issue: 1 Pages: 161-170
  • DOI: 10.1016/j.bbrc.2019.08.025
  • Peer Reviewed / Open Access
• [Journal Article] Iron Supply via NCOA4-Mediated Ferritin Degradation Maintains Mitochondrial Functions (2019)
  • Author(s): Fujimaki Motoki、Furuya Norihiko、Saiki Shinji、Amo Taku、Imamichi Yoko、Hattori Nobutaka
  • Journal Title: Molecular and Cellular Biology Volume: 39 Issue: 14
  • DOI: 10.1128/mcb.00010-19
  • Peer Reviewed / Open Access
• [Journal Article] p150glued deficiency impairs effective fusion between autophagosomes and lysosomes due to their redistribution to the cell periphery. (2019)
  • Author(s): Ishikawa-KI, Saiki S, Furuya N, Imamichi Y, Tsuboi Y, Hattori N
  • Journal Title: Neuroscience Letters Volume: 690 Pages: 181-187
  • DOI: 10.1016/j.neulet.2018.10.036
  • Peer Reviewed / Open Access
• [Journal Article] Zonisamide Administration Improves Fatty Acid β-Oxidation in Parkinson's Disease. (2018)
  • Author(s): Ueno SI, Saiki S, Fujimaki M, Takeshige-Amano H, Hatano T, Oyama G, Ishikawa KI, Yamguchi A, Nojiri S, Akamatsu W, Hattori N.
  • Journal Title: Cells Volume: 8 Issue: 1 Pages: 14-14
  • DOI: 10.3390/cells8010014
  • Peer Reviewed / Open Access
• [Journal Article] NDP52 interacts with mitochondrial RNA poly(A) polymerase to promote mitophagy. (2018)
  • Author(s): Furuya N, Kakuta S, Sumiyoshi K, Ando M, Nonaka R, Suzuki A, Kazuno S, Saiki S, Hattori N.
  • Journal Title: EMBO Reports Volume: 19 Issue: 12
  • DOI: 10.15252/embr.201846363
  • Peer Reviewed / Open Access
• [Presentation] New Biomarkers for Parkinson’s disease (2019)
  • Author(s): Shinji Saiki
  • Organizer: 6th Asian and Oceanian Parkinson’s Disease and Movement Disorders Congress
  • Int'l Joint Research / Invited
• [Presentation] パーキンソン病の代謝産物バイオマーカーについて (2019)
  • Author(s): 斉木臣二
  • Organizer: 第13回パーキンソン病・運動障害疾患コングレス
  • Invited
• [Presentation] Blood metabolic biomarkers for Parkinson's disease (2019)
  • Author(s): Shinji Saiki
  • Organizer: 9th Biennial Meeting of Society for Free Radical Research-Asia
  • Int'l Joint Research / Invited
• [Presentation] Development of anti-Parkinson’s disease medicines focusing on autophagy/mitophagy modulation (2018)
  • Author(s): Shinji Saiki
  • Organizer: 第61回日本神経化学会大会・第40回日本生物学的精神医学会
  • Invited
• [Remarks] 化合物による治療探索研究・オートファジー関連研究
  • URL: https://www.juntendo-neurology.com/
• [Remarks] 化合物による治療探索研究・オートファジー関連研究
  • URL: http://www.juntendo-neurology.com/n-kenkyu-syoukai.html
• [Remarks] 化合物による治療探索研究・オートファジー関連研究
  • URL: http://www.juntendo-neurology.com/pdf/saiki2015.pdf