Zinc effect for iron efflux from the neuronal cells

• Project/Area Number: 26461291
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Miyajima Hiroaki 浜松医科大学, 医学部, 教授 (90221613)
• Co-Investigator(Kenkyū-buntansha): 河野 智 浜松医科大学, 医学部附属病院, 講師 (40397386)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 鉄 / 亜鉛 / フェロポルチン / セルロプラスミン / トランスフェリン / 亜鉛トランスポーター / マンガン / 鉄酸化作用 / 酸化ストレス / 無セルロプラスミン血症 / 神経変性 / ヘプシジン / ヘファエスチン / アストロサイト

Outline of Final Research Achievements

Zinc can play an important role in the stability of ferroportin and ferrous iron binding to transferrin. We found that zinc transporter ZnT10 is localized to the plasma membrane and functional in Mn metabolism by effluxing cytosolic Mn. Because zinc has antioxidant activity, treatment with zinc may be useful in patients with neurodegeneration with brain iron accumulation to diminish iron accumulation in the brain.

Research Products

• [Journal Article] Direct comparison of manganese detoxification/efflux proteins and molecular characterization of ZnT10 protein as a manganese transporter. (2016)
  • Author(s): Nishito Y, Tsuji N, Fujishiro H, Takeda TA, Yamazaki T, Teranishi F, Okazaki F, Matsunaga A, Tuschl K, Rao R, Kono S, Miyajima H, Narita H, Himeno S, Kambe T.
  • Journal Title: J Biol Chem Volume: 291 Pages: 14773-14787
  • NAID: 120006376011
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Copper accumulates in hemosiderins in livers of patients with iron overload syndromes. (2015)
  • Author(s): Ono Y, Ishigami M, Hayashi K, Wakusawa S, Hayashi H, Kumagai K, Morotomi N, Yamashita T, Kawanaka M, Watanabe M, Ozawa H, Tai M, Miyajima H, Yoshioka K, Hirooka Y, Goto H.
  • Journal Title: J Clin Transl Hepatol Volume: 3 Pages: 85-92
  • Peer Reviewed
• [Journal Article] Investigated and available therapeutic options for treating aceruloplasminemia. (2015)
  • Author(s): Miyajima H
  • Journal Title: Expert Opinion on Orphan Drugs Volume: 3 Issue: 9 Pages: 1011-1020
  • DOI: 10.1517/21678707.2015.1067137
  • Peer Reviewed / Open Access
• [Journal Article] Aceruloplasminemia (2015)
  • Author(s): Miyajima H
  • Journal Title: Neuropathol Volume: 35 Pages: 83-90
  • NAID: 10008311253
  • Peer Reviewed / Open Access
• [Journal Article] Case of presymptomatic aceruloplasminemia treated with deferasirox (2014)
  • Author(s): Tai M, Matsuhashi N, Ichii O, Suzuki T, Ejiri Y, Kono S, Terada T, Miyajima H, Harada M
  • Journal Title: Hepatol Res Volume: 44 Pages: 1253-1258
  • Peer Reviewed / Open Access
• [Presentation] 鉄代謝の解明に向けて～新たな創薬のターゲット～ (2015)
  • Author(s): 宮嶋裕明
  • Organizer: 第33回日本神経治療学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-11-26
  • Invited
• [Presentation] Aceruloplasminemia (2014)
  • Author(s): Miyajima H
  • Organizer: 55th Annual Meeting of JSNP
  • Place of Presentation: Tokyo
  • Year and Date: 2014-06-05 – 2014-06-07
  • Invited
• [Book] Annual Review 神経 2017 (2017)
  • Author(s): 河野智、宮嶋裕明
  • Total Pages: 281
  • Publisher: 中外医学社
• [Book] 鉄剤の適正使用による貧血治療指針. 改訂[第３版] (2015)
  • Author(s): 林久男、宮嶋裕明
  • Total Pages: 96
  • Publisher: 響文社
• [Book] Rosenberg’s Molecular and Genetic Basis of Neurological and Psychiatric Disease. (2015)
  • Author(s): Kono S, Miyajima H
  • Publisher: Elsevier, Academic Press