Involvement of NUB1 in the early phase of Lewy body disease

• Project/Area Number: 26430050
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Hirosaki University
• Principal Investigator: TANJI Kunikazu 弘前大学, 医学研究科, 助教 (10271800)
• Co-Investigator(Kenkyū-buntansha): 若林 孝一 弘前大学, 医学研究科, 教授 (50240768)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 脳神経疾患 / レビー小体病 / シャペロン分子 / レビー小体型認知症 / 分解システム / 神経変性 / リン酸化 / 凝集 / 神経変性疾患 / タンパク質分解 / アルツハイマー病 / パーキンソン病

Outline of Final Research Achievements

Abnormal α-synuclein (Syn) is deposited in neuronal cytoplasmic inclusions and presynapses in Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Previously we have shown that NUB1 is accumulated in these specific regions together with abnormal Syn and that NUB1 is able to inhibit α-synuclein aggregation in cultured cells. We therefore created transgenic (Tg) mice expressing both NUB1 and abnormal Syn to investigate the role of NUB1 on degradation of abnormal Syn in vivo. Immunohistochemical and biochemical studies confirmed that NUB1 was over-expressed in neurons of mice expressing NUB1 (NUB1 Tg), and both NUB1 and abnormal Syn (double Tg). Normal and abnormal Syn levels were unchanged between abnormal Syn Tg mice (Lewy body disease model mice) and double Tg mice. Pathological observations were almost similar between them. Biochemical analysese showed that level of insoluble Syn were lower in double Tg mice compared with abnormal Syn Tg mice.

Research Products

• [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (2016)
  • Author(s): Klionsky DJ., Abdelmohsen K., Abe A., Abedin MJ.,Inomata M., et al.
  • Journal Title: Autophagy Volume: 12(1) Issue: 1 Pages: 1-222
  • DOI: 10.1080/15548627.2015.1100356
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Alteration of Upstream Autophagy-Related Proteins (ULK1, ULK2, Beclin1, VPS34 and AMBRA1) in Lewy Body Disease (2016)
  • Author(s): Miki Y, Tanji K, Mori F, Utsumi J, Sasaki H, Kakita A, Takahashi H, Wakabayashi K.
  • Journal Title: Brain Pathol Volume: - Issue: 3 Pages: 359-370
  • DOI: 10.1111/bpa.12297
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The role of NUB1 in alpha-synuclein degradation in Lewy body disease model mice (2016)
  • Author(s): Tanji K, Miki Y, Maruyama A, Mori F, Mimura J, Itoh K, Kamitani T, Wakabayashi K.
  • Journal Title: Biochem Biophys Res Commun Volume: 470 Issue: 3 Pages: 635-642
  • DOI: 10.1016/j.bbrc.2016.01.093
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] レビー小体病におけるsynphilin-1結合タンパク質（NUB1）の役割 The role of NUB1 in abnormal alpha-synuclein status in vivo, (2016)
  • Author(s): 丹治邦和, 三木康生, 丸山敦史, 森 文秋, 三村純正, 伊東 健, 神谷 哲, 若林孝一
  • Organizer: 第57回日本神経病理学会,
  • Place of Presentation: ホテルニューキャッスル（青森 弘前市)
  • Year and Date: 2016-06-01
• [Presentation] レビー小体病におけるsynphilin-1結合タンパク質（NUB1）の役割 (2016)
  • Author(s): 丹治邦和, 三木康生, 丸山敦史, 森 文秋, 三村純正, 伊東 健, 神谷 哲, 若林孝一
  • Organizer: 第57回日本神経病理学会
  • Place of Presentation: ホテルニューキャッスル（青森県・弘前市）
  • Year and Date: 2016-06-01