Investigation of lipid metabolism in Parkinson's disease

• Project/Area Number: 18K15376
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Juntendo University
• Principal Investigator: Mori Akio 順天堂大学, 医学部, 非常勤助教 (60782878)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: パーキンソン病 / α-シヌクレイン / 神経変性疾患 / 脂質代謝異常 / リン脂質 / 異常タンパク質 / ショウジョウバエ / エクソソーム / 脂質代謝破綻 / PLA2G6 / PLA2G６ / 疾患修飾治療 / 神経変性 / リポソーム / 凝集体形成 / 生体膜 / シナプス小胞

Outline of Final Research Achievements

PLA2G6 gene is a causative gene of Parkinson's disease with α-synucleinopathy. We reported that PLA2G6-deficient Drosophila exhibits defects in neurotransmission, progressive cell loss, and aggregation of α-synuclein. Lipid analysis of the brain reveals that alternation in phospholipids. We reported these results Proceedings of the National Academy of Sciences of the United States of America (PNAS). Recently, we found abnormal exosomes from PLA2G6 knock-out cells. This result also suggests that lipid alteration leads to abnormal clearance.

Academic Significance and Societal Importance of the Research Achievements

パーキンソン病は現在までのところ，疾患修飾治療は存在しない．我々は新たに脂質代謝に注目した．脂質改変により神経変性を予防することを動物モデルで明らかにしたことにより，疾患治療や食事を通した予防医学に通じる研究成果であると考える．

Research Products

• [Journal Article] The identified clinical features of Parkinson's disease in homo-, heterozygous and digenic variants of PINK1 (2021)
  • Author(s): Hayashida Arisa、Li Yuanzhe、Yoshino Hiroyo、Daida Kensuke、Ikeda Aya、et al.
  • Journal Title: Neurobiology of Aging Volume: 97 Pages: 3301-3301
  • DOI: 10.1016/j.neurobiolaging.2020.06.017
  • Peer Reviewed / Open Access
• [Journal Article] Nonmercaptalbumin as an oxidative stress marker in Parkinson's and PARK2 disease (2020)
  • Author(s): Ueno SI, Hatano T, Okuzumi A, Saiki S, Oji Y, Mori A, Koinuma T, Fujimaki M, Takeshige-Amano H, Kondo A, Yoshikawa N, Nojiri T, Kurano M, Yasukawa K, Yatomi Y, Ikeda H, Hattori N
  • Journal Title: Ann Clin Transl Neurol Volume: 7 Issue: 3 Pages: 307-317
  • DOI: 10.1002/acn3.50990
  • Peer Reviewed / Open Access
• [Journal Article] Lipids: Key Players That Modulate -Synuclein Toxicity and Neurodegeneration in Parkinson’s Disease (2020)
  • Author(s): Akio Mori, Yuzuru Imai, Nobutaka Hattori
  • Journal Title: International Journal of Molecular Sciences Volume: 21 Issue: 9 Pages: 9-9
  • DOI: 10.3390/ijms21093301
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Parkinson's disease-associated iPLA2-VIA/PLA2G6 regulates neuronal functions and α-synuclein stability through membrane remodeling. (2019)
  • Author(s): Mori A, Hatano T, Inoshita T, Shiba-Fukushima K, Koinuma T, Meng H, Kubo SI, Spratt S, Cui C, Yamashita C, Miki Y, Yamamoto K, Hirabayashi T, Murakami M, Takahashi Y, Shindou H, Nonaka T, Hasegawa M, Okuzumi A, Imai Y, Hattori N.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 116(41) Issue: 41 Pages: 20689-20699
  • DOI: 10.1073/pnas.1902958116
  • NAID: 120007132272
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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
• [Presentation] Disease Modifying Therapy in PD (2020)
  • Author(s): 森 聡生
  • Organizer: 第19回高松国際パーキンソン病シンポジウム
  • Invited
• [Presentation] Disease Modifying Therapy in PD (2020)
  • Author(s): Akio Mori
  • Organizer: Takamatsu International Symposium for PD ＆MD
  • Int'l Joint Research / Invited
• [Presentation] MSAとPSPの血漿バイオマーカー (2019)
  • Author(s): 森 聡生
  • Organizer: パーキンソン病・運動障害疾患コングレス
• [Presentation] Synaptic dysfuncion in a Drosophila model of PARK14 (2019)
  • Author(s): T. Hatano, A. Mori, T. Inoshita, K. Fukushima-Shiba, T. Koinuma, C. Yamashita, Y. Imai, N. Hattori
  • Organizer: International Parkinson and Movement disorder society 2019
  • Int'l Joint Research
• [Presentation] Parkinson's disease-associated mutations of PLA2G6 alters the membrane dynamics and α-synuclein stability (2019)
  • Author(s): A. Mori, T. Hatano, T. Inoshita, K. Shiba-Fukushima, T. Koinuma, C. Yamashita, A. Okuzumi, Y. Imai, N. Hattori
  • Organizer: International Parkinson and Movement disorder society 2019
  • Int'l Joint Research
• [Presentation] リン脂質リモデリング異常はシナプス機能異常と α-シヌクレイン凝集を引き起こす (2019)
  • Author(s): 森 聡生
  • Organizer: 第17回神経科学研究会
  • Invited
• [Presentation] Parkinson's disease-associated iPLA2-VIA regulates the remodeling of phospholipid membrane, which is important for dopaminergic functions and α-Synuclein turnover (2018)
  • Author(s): 森 聡生
  • Organizer: 日本神経科学大会
• [Presentation] 脂質改変治療はパーキンソン病の 新たな疾患修飾治療になる (2018)
  • Author(s): 森 聡生
  • Organizer: 神経治療学会学術集会
• [Presentation] 抗MOG抗体関連疾患の髄液MBP値は病変の広がりと相関する (2018)
  • Author(s): 森 聡生
  • Organizer: 日本神経免疫学会学術集会
• [Book] CLINICAL NEUROSCIENCE (2019)
  • Author(s): 水澤 英洋
  • Total Pages: 128
  • Publisher: 中外医学社
• [Remarks] 脳内の脂質変化がパーキンソン病の原因となるメカニズムを解明
  • URL: https://www.amed.go.jp/news/release_20190927-01.html
• [Remarks] 脳内の脂質変化がパーキンソン病の原因となるメカニズムを解明
  • URL: https://www.juntendo.ac.jp/news/20190927-02.html