Effect of ATBF1 on the neuronal death and APP trafficking using ATBF1 KO mouse

• Project/Area Number: 15K06714
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: Nagoya City University
• Principal Investigator: Jung Cha-Gyun 名古屋市立大学, 大学院医学研究科, 准教授 (00464579)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: アルツハイマー病 / ATBF1 / APP代謝 / Aβ産生 / 神経細胞死

Outline of Final Research Achievements

In the present study, we determined the functional role of ATBF1 in neuronal death using ATBF1 knockout mouse. The density of TUNEL positive and activated caspase3 positive cells was comparable between brains of wild-type and knockout mice at E19. However, cultured cortical neurons isolated from ATBF1 KO mice protected against neuronal death induced by Aβ42 compared with wild-type mice. Moreover, ATBF1 binds to Smad2,3,4 for down-regulating Bcl2 (pro-apoptotic factor) expression, thereby inhibiting neuronal death. Our findings suggest that ATBF1 may be a suitable target for therappeutic intervention of AD.

Research Products

• [Int'l Joint Research] Cellular Aging and Neurodegeneration/Ilsong Institute of Life Science/Hallym University(韓国)
• [Int'l Joint Research] Department of Microbiology/College of Medicine/Hallym University(韓国)
• [Int'l Joint Research] Cellular Aging and Neurodegeneration/Ilsong Institute of Life Science/Hallym University(韓国)
• [Int'l Joint Research] Department of Microbiology/College of Medicine/Hallym University(韓国)
• [Journal Article] A novel biosensor with high signal-to-noise ratio for real-time measurement of dopamine levels in vivo. (2018)
  • Author(s): Ishida A, Imamura A, Ueda Y, Shimizu T, Marumoto R, Jung CG, Hida H
  • Journal Title: J Neurosci Res Volume: 96 Issue: 5 Pages: 817-827
  • DOI: 10.1002/jnr.24193
  • Peer Reviewed / Open Access
• [Journal Article] Disorganization of oligodendrocyte development in the layer II/III of the sensorimotor cortex causes motor coordination dysfunction in a model of white matter injury in neonatal rats (2018)
  • Author(s): Ueda Y, Misumi S, Suzuki M, Ogawa S, Nishigaki R, Ishida A, Cha-Gyun Jung, Hida H.
  • Journal Title: Neurochemical Research Volume: 43(1) Issue: 1 Pages: 127-37
  • DOI: 10.1007/s11064-017-2352-3
  • Peer Reviewed
• [Journal Article] A diagnostic marker for superficial urothelial bladder carcinoma: lack of nuclear ATBF1 (ZFHX3) by immunohistochemistry suggests malignant progression. (2016)
  • Author(s): Kawaguchi M, Hara N, Bilim V, Koike H, Suzuki M, Kim TS, Gao N, Dong Y, Zhang S, Fujinawa Y, Yamamoto O, Ito H, Tomita Y, Naruse Y, Sakamaki A, Ishii Y, Tsuneyama K, Inoue M, Itoh J, Yasuda M, Sakata N, Jung CG, Kanazawa S, Akatsu H, Minato H, Nojima T, Asai K, Miura Y.
  • Journal Title: BMC Cancer. Volume: 16 Issue: 1 Pages: 805-805
  • DOI: 10.1186/s12885-016-2845-5
  • NAID: 120006814095
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dysfunction in Motor Coordination in Neonatal White Matter Injury Model without Apparent Neuron Loss (2015)
  • Author(s): Misumi S, Ueda Y, Nishigaki R, Suzuki M, Ishida A, Jung CG, Hida H.
  • Journal Title: Cell Transplantation Volume: Nov 11 Issue: 7 Pages: 1381-93
  • DOI: 10.3727/096368915x689893
  • Peer Reviewed / Open Access
• [Journal Article] ATBF1 is a novel amyloid-β protein precursor protein (AβPP) binding protein that affects APP expression (2015)
  • Author(s): Uhm KO, Kim MJ, Kawaguchi M, Akatsu H, Miura Y, Misumi S, Hida H, Choi EK, Kim YS, Michikawa M, Jung CG.
  • Journal Title: J Alzheimers Dis Volume: 43 Issue: 1 Pages: 243-257
  • DOI: 10.3233/jad-140612
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Auraptene increases the production of amyloid-beta via c-Jun N-terminal kinase-dependent activation of γ-secretase. (2015)
  • Author(s): Jung CG, Uhm KO, Horike H, Kim MJ, Misumi S, Ishida A, Ued Y, Choi EK, Kim YS, Michikawa M, Hida H.
  • Journal Title: J Alzheimers Dis Volume: 43 Issue: 4 Pages: 1215-1228
  • DOI: 10.3233/jad-141692
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Early constraint-induced movement therapy promotes functional recovery and neuronal plasticity in a subcortical hemorrhage model rat (2015)
  • Author(s): Ishida Akimasa, Misumi Sachiyo, Ueda Yoshitomo, Shimizu Yuko, Cha-Gyun Jung, Tamakoshi Keiji, Ishida Kazuto, Hida Hideki
  • Journal Title: Behavioral brain research Volume: 284 Pages: 158-166
  • DOI: 10.1016/j.bbr.2015.02.022
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Phosphatidylinositol-Glycan-Phospholipase D is Involved in Neurodegeneration in Prion Disease. (2015)
  • Author(s): Jin JK, Jang BG, Choi EK, Jung CG, Akatsu H, Kim JI, Carp RI, Kim YS
  • Journal Title: PLoS One Volume: 13 Issue: 4 Pages: e0122120-e0122120
  • DOI: 10.1371/journal.pone.0122120
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Arachidonic Acid Diet Attenuates Aβ Deposition in Tg2576 Mice. (2015)
  • Author(s): Hosono T, Nishitsuji K, Nakamura T, Jung CG, Kontani M, Tokuda H, Kawashima H, Kiso Y, Suzuki T, Michikawa M
  • Journal Title: Brain Res Volume: 10 Pages: 1613-1629
  • DOI: 10.1016/j.brainres.2015.04.005
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Arachidonic or docosahexaenoic acid diet prevents memory impairment in Tg2576 mice. (2015)
  • Author(s): Hosono T, Mouri A, Nishitsuji K, Jung CG, Kontani M, Tokuda H, Kawashima H, Shibata H, Suzuki T, Nabeshima T, Michikawa M.
  • Journal Title: J Alzheimers Dis Volume: 48 Issue: 1 Pages: 149-162
  • DOI: 10.3233/jad-150341
  • Peer Reviewed / Int'l Joint Research
• [Presentation] ATBF1 is a novel APP binding protein that affects APP level (2018)
  • Author(s): 鄭 且均、川口 誠、赤津 裕康、道川誠
  • Organizer: 日本認知症学会
• [Presentation] Cellular Prion Protein Inhibits Cell Death via Regulation of ATBF1 and Its Related Signaling Pathway (2016)
  • Author(s): Han SS, Choi HS, Park JH, Kim HJ, Jun YC, Kim YS, Jung CG, Choi EK
  • Organizer: 2016年第２４回基礎医学学術第会
  • Place of Presentation: 仁川（韓国）
• [Presentation] Protection of ATBF1-mediated Neuronal Cell Death by Cellular Prion Protein (2016)
  • Author(s): Han SS, Choi HS, Park JH, Kim HJ, Jun YC, Kim YS, Jung CG, Choi EK
  • Organizer: ２０１６年韓国人老人科学学術団体連合会学術第会
  • Place of Presentation: ソウル（韓国）