Expression analysis of ubiquitin ligase HRD1 in neurodegenerative disorders and application to forensic neuropathology

• Project/Area Number: 23790722
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Legal medicine
• Research Institution: Kyoto University (2012); Asahikawa Medical College (2011)
• Principal Investigator: OMURA Tomohiro 京都大学, 医学研究科, 特定職員 (00439035)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 神経化学 / 小胞体ストレス / HRD1 / 脳機能障害 / 国際研究者交流 / ドイツ / オーストリア / アメリカ

Research Abstract

HRD1 is reported to be involved in the pathogenesis of neurodegenerative disorders by its ubiquitin ligase activity. In the present study, we examine whether it is possible for HRD1 to be the marker of brain dysfunction. We found that HRD1 and related molecules are induced in the in vitromodels of neurodegenerative disorders. Furthermore, we demonstrated that zonisamide, an antiepileptic agent, up-regulates HRD1 and suppresses neuronal cell death.

Research Products

• [Journal Article] Endoplasmic Reticulum Stress and Parkinson’s Disease: The Role of HRD1 in Averting Apoptosis in Neurodegenerative Disease (2013)
  • Author(s): Omura T, Kaneko M, Okuma Y, Matsubara K, and Nomura Y
  • Journal Title: Oxid Med Cell Longev Volume: 2013 Pages: 239854-239854
  • DOI: 10.1155/2013/239854
  • Peer Reviewed
• [Journal Article] メロキシカムは,マウスパーキンソン病モデルにおいて,Akt シグナル維持により運動障害とドパミン神経変性を改善する (2013)
  • Author(s): 田崎嘉一,山本譲,大村友博,坂口智己,木村周古,大滝康一,小野尚志,須野学,浅利優,大久保知子,野田敏宏,粟屋敏雄,清水惠子,松原和夫
  • Journal Title: 北海道医誌 Volume: 88(1) Pages: 45-45
  • NAID: 10031148191
  • Peer Reviewed
• [Journal Article] ゾニサミドによるHRD1の増加が，神経細胞SH-SY5Yにおける小胞体ストレス誘発細胞死とカスパーゼ-3の活性化を抑制する． (2013)
  • Author(s): 大村友博
  • Journal Title: 北海道医学雑誌 Volume: 87 Pages: 251-251
  • NAID: 10031131092
  • Peer Reviewed
• [Journal Article] ゾニサミドによる HRD1 の増加が,神経細胞 SH-SY5Y における小胞体ストレス誘発細胞死とカスパーゼ-3 の活性化を抑制する (2012)
  • Author(s): 大村友博,浅利優,山本譲,神山直也,岡久美子,保科千里,間瀬田千香暁,粟屋敏雄,田崎嘉一,塩野寛,清水惠子,松原和夫
  • Journal Title: 北海道医誌 Volume: 87(6) Pages: 251-251
  • NAID: 10031131092
  • Peer Reviewed
• [Journal Article] Meloxicam ameliorates motor dysfunction and dopaminergic neurodegeneration by maintaining Akt-signaling in a mouse Parkinson's disease model. (2012)
  • Author(s): Tasaki Y, Yamamoto J, Omura T, Sakaguchi T, Kimura N, Ohtaki K, Ono T, Suno M, Asari M, Ohkubo T, Noda T, Awaya T, Shimizu K, Matsubara K.
  • Journal Title: Neurosci. Lett. Volume: 521 Pages: 15-19
  • DOI: 10.1016/j.neulet.2012.05.045
  • NAID: 120006522757
  • Peer Reviewed
• [Journal Article] HRD1 Levels Increased by Zonisamide Prevented Cell Death and Caspase-3 Activation Caused by Endoplasmic Reticulum Stress in SH-SY5Y Cells (2012)
  • Author(s): Omura T, Asari M, Yamamoto J, Kamiyama N, Oka K, Hoshina C, Maseda C, Awaya T, Tasaki Y, Shiono H, Shimizu K, Matsubara K
  • Journal Title: Journal of Molecular Neuroscience Volume: 46(3) Pages: 527-535
  • DOI: 10.1007/s12031-011-9638-8
  • NAID: 10031131092
  • Peer Reviewed
• [Journal Article] Oxicam structure in non-steroidal anti-inflammatory drugs is essential to exhibit Akt-mediated neuroprotection against 1-methyl-4- phenyl, pyridinium-induced cytotoxicity. (2012)
  • Author(s): Tasaki Y, Yamamoto J, Omura T, Noda T, Kamiyama N, Yoshida K, Satomi M, Sakaguchi T, Asari M, Ohkubo T, Shimizu K, Matsubara K.
  • Journal Title: Eur. J. Pharmacol Volume: 676 Pages: 57-63
  • DOI: 10.1016/j.ejphar.2011.11.046
  • NAID: 120006522756
  • Peer Reviewed
• [Presentation] Myeloid cell leukemia-1 (Mcl-1) は SH-SY5Y 細胞のMPP+誘発アポトーシスに対して保護作用を持つ (2013)
  • Author(s): 田崎嘉一,吉田光一,小野尚志,山本譲,坂口智己,飯田慎也,大滝康一,神山直也,木村周古,大久保知子,野田敏宏,大村友博,粟屋敏雄,松原和夫
  • Organizer: 日本薬学会第133 年会
  • Place of Presentation: 横浜
• [Presentation] オキシカム系 NSAIDsは、MPTP 反復投与パーキンソン病モデルにおいて黒質線条体神経を保護し、行動異常を改善する (2012)
  • Author(s): 田崎嘉一,山本譲,坂口智己,野田敏宏,大村友博,神山直也,吉田光一,大久保知子,松原和夫
  • Organizer: 日本薬学会第132 年会
  • Place of Presentation: 札幌
• [Presentation] Oxicam non-steroidal anti-inflammatory drugs ameliorate motor dysfunction and dopaminergic degeneration by maintaining Akt-signaling in a mouse Parkinson's disease model (2012)
  • Author(s): Tasaki Y, Yamamoto J, Ohkubo T, Noda T, Omura T, Ono T, Kimura N, Suno M, Sakaguchi T, Matsubara K.
  • Organizer: Neuroscience 2012
  • Place of Presentation: New Orleans, USA
• [Presentation] Structural specificity of Akt-mediated neuroprotection by oxicam non-steroidal anti-inflammatory drugs against 1-methyl-4-phenyl pyridinium-induced cell death (2011)
  • Author(s): Tasaki Y, Yamamoto J, Omura T, Noda T, Kamiyama N, Yoshida K, Satomi M, Sakaguchi T, Asari M, Ohkubo T, Shimizu K, Matsubara K
  • Organizer: WFN World Congress on Parkinson's Disease and Related Disorders 2011
  • Place of Presentation: Shanghai, China
• [Presentation] Zonisamide increases human HRD1 protein resulting in the repression of caspase-3 activation and cell death caused by the ER stress in SH-SY5Y cells (2011)
  • Author(s): Omura T, Asari M, Tasaki Y, Hoshina C, Yamamoto J, Kamiyama N, Oka K, Matsuda T, Kitamura A, Maseda C, Shimizu K, Matsubara K.
  • Organizer: Neuroscience 2011
  • Place of Presentation: Washington DC, USA
• [Presentation] Zonisamide increases human HRD1 protein resulting in the repression of caspase-3 activation and cell death caused by the ER stress in SH-SY5Y cells (2011)
  • Author(s): Tomohiro Omura
  • Organizer: Society for Neuroscience 41st Annual Meeting
  • Place of Presentation: Walter E Washington Convention Center
• [Book] A)精神・脳神経系疾患 3 章.パーキンソン病 (2011)
  • Author(s): 大村友博,松原和夫
  • Publisher: 日本医療薬学会 [南江堂]