Development of biomarker based on the pathogenesis of Parkinson's disease

• Project/Area Number: 15K06780
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Juntendo University
• Principal Investigator: SATO SHIGETO 順天堂大学, 医学部, 准教授 (00445537)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: パーキンソン病 / Parkin / ミトコンドリア / 神経変性疾患 / バイオマーカー / 認知症 / リン酸化 / PINK1 / マウス / CCCP / Ｐａｒｋｉｎ / Atp13a2 / リソソーム

Outline of Final Research Achievements

Abnormal mitochondrial accumulation leads to cell dysfunction and causes various pathological conditions such as cancer and degenerative diseases. At that time, it is speculated that the defective mitochondrial removal mechanism is triggered. Phosphorylation signals for activation of removal mechanisms, which have been clarified in in vitro systems, can be indicators of neurodegeneration. As a result of searching the brain pathology sample, it was suggested that the phosphorylation of Parkin is enhanced in the neuronal cells causing neurofibrillary tangles.

Academic Significance and Societal Importance of the Research Achievements

In vitroで明らかになりつつある不良ミトコンドリア除去機構が実際に生体内で機能しているかは不明であり今後のさらなる研究が必要である。認知症病理標本でリン酸化シグナルが亢進しているとの本研究結果は認知症の病態解明に迫るものであると同時に新たなバイオマーカーを提案するものである。

Research Products

• [Journal Article] Dopaminergic Neuron-Specific Autophgy-Deficient Mice. (2018)
  • Author(s): Sato S, Hattori N
  • Journal Title: Methods Mol Biol. Volume: 1759 Pages: 173-175
  • Peer Reviewed / Open Access
• [Journal Article] Loss of autophagy in dopaminergic neurons causes Lewy pathology and motor dysfunction in aged mice. (2018)
  • Author(s): Sato S, Uchihara T, Fukuda T, Noda S, Kondo H, Saiki S, Komatsu M, Uchiyama Y, Tanaka K, Hattori N.
  • Journal Title: Sci Rep. Volume: ８ Issue: 1 Pages: 2813-2813
  • DOI: 10.1038/s41598-018-21325-w
  • Peer Reviewed / Open Access
• [Journal Article] Lysosomal storage of subunit c of mitochondrial ATP synthase in brain-specific Atp13a2-deficient mice. (2016)
  • Author(s): Sato S
  • Journal Title: Am. J. Pathol Volume: 186 Pages: 3074-3082
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Functional Neurons Generated from T Cell-Derived Induced Pluripotent Stem Cells (2016)
  • Author(s): Matsumoto T, Fujimori K, Andoh-Noda T, Ando T, Kuzumaki N, Toyoshima M, Tada H, Imaizumi K, Ishikawa M, Yamaguchi R, Isoda M, Zhou Z, Sato S, Kobayashi T, Ohtaka M, Nishimura K, Kurosawa H, Yoshikawa T, Takahashi T, Nakanishi M, Ohyama M, Hattori N, Akamatsu W, Okano H.
  • Journal Title: Stem Cell Reports. Volume: 6 Issue: 3 Pages: 422-35
  • DOI: 10.1016/j.stemcr.2016.01.010
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Pathological perspective on autophagy lysosomal pathway in Parkinson’s disease (2015)
  • Author(s): 佐藤栄人
  • Organizer: GEO-PD
  • Place of Presentation: 六本木アカデミーヒルズ
  • Year and Date: 2015-10-01
  • Int'l Joint Research / Invited