Investigation of the relationship between autophagy and NBIA causative genes.

• Project/Area Number: 15K09325
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Juntendo University
• Principal Investigator: Furuya Norihiko 順天堂大学, 医学(系)研究科(研究院), 助教 (50401188)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: オートファジー / NBIA / 鉄代謝 / フェリチン / フェリチノファジー / ミトコンドリア / 酸化ストレス / リソソーム

Outline of Final Research Achievements

Neurodegeneration with brain iron accumulation (NBIA) is a set of degenerative extrapyramidal monogenic disorders with radiological evidence of focal accumulation of iron in the brain, usually in the basal ganglia. In this study, we investigated the relationship between autophagy and NBIA causative genes. Knockdown using siRNA of a part of NBIA genes influenced autophagy or lysosomal system. To investigate those genes function more precisely, we tried to establish knockout (KO) cell lines using CRISPR/Cas9 system. We could successfully obtain FTL KO cells. FTL KO cells showed the reduction of ferritin-selective autophagy (ferritinophagy) flux, the reduction of mitochondrial function and the vulnerability against oxidative stress. Those phenotypes of FTL KO cells must tightly associate with the mechanism of NBIA disease onset.

Research Products

• [Journal Article] Decreased long-chain acylcarnitines from insufficient β-oxidation as potential early diagnostic markers for Parkinson's disease. (2017)
  • Author(s): Saiki S, Hatano T, Fujimaki M, Ishikawa K, Mori A, Oji Y, Okuzumi A, Fukuhara T, Koinuma T, Nagumo M, Furuya N, Nojiri S, Amo T, Yamashiro K, Hattori N.
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 7328-7328
  • DOI: 10.1038/s41598-017-06767-y
  • Peer Reviewed / Open Access
• [Journal Article] VPS29-VPS35 intermediate of retromer is stable and may be involved in the retromer complex assembly process. (2015)
  • Author(s): Fuse A, Furuya N, Kakuta S, Inose A, Sato M, Koike M, Saiki S, Hattori N
  • Journal Title: FEBS Lett. Volume: 589 Issue: 13 Pages: 1430-1436
  • DOI: 10.1016/j.febslet.2015.04.040
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Ethambutol neutralizes lysosomes and causes lysosomal zinc accumulation. (2015)
  • Author(s): Yamada D, Saiki S, Furuya N, Ishikawa K, Imamichi Y, Kambe T, Fujimura T, Ueno T, Koike M, Sumiyoshi K, Hattori N
  • Journal Title: Biochem Biophys Res Commun. Volume: 471 Issue: 1 Pages: 109-116
  • DOI: 10.1016/j.bbrc.2016.01.171
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] NDP52を介したマイトファゴソーム形成機構の解析 (2016)
  • Author(s): 古屋徳彦
  • Organizer: 第4回新学術「オートファジー」班会議、第10回オートファジー研究会
  • Place of Presentation: 新潟県南魚沼郡湯沢町
  • Year and Date: 2016-11-14
• [Presentation] マイトファジーにおけるNDP52-LC3C経路の解析 (2015)
  • Author(s): 古屋徳彦
  • Organizer: 第9回オートファジー研究会・第3回「オートファジー」班会議
  • Place of Presentation: 兵庫県淡路市
  • Year and Date: 2015-11-16
• [Book] Methods Mol Biol. (2017)
  • Author(s): Furuya N
  • Publisher: Springer
• [Book] Methods Mol Biol. (2017)
  • Author(s): Sato S, Furuya N.
  • Publisher: Springer
• [Book] Methods in Molecular Biology "Induction of PINK1/Parkin-Mediated Mitophagy" (2017)
  • Author(s): Sato S, Furuya N
  • Total Pages: 9
  • Publisher: Springer