Development of oxicam-bearing non-steroidal anti-inflammatory drugs with novel anti-parkinsonian mechanism.

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590129
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Asahikawa Medical College
• Principal Investigator: TASAKI Yoshikazu 旭川医科大学, 医学部, 准教授 (60374807)
• Co-Investigator(Kenkyū-buntansha): MATSUBARA Kazuo 旭川医科大学, 医学部, 教授 (20127533) ; MATSUBARA Kazuo 京都大学, 医学部, 教授 (20127533)
• Project Period (FY): 2010 – 2012
• Keywords: 臨床薬学 / パーキンソン病進行抑制薬

Research Abstract

In this study, three oxicam-bearing non-steroidal anti-inflammatroy drugs(NSAIDs), such as meloxicam, piroxicam and tenoxicam, were identified to have novel neuroprotective mechanism of maintaining phosphatidylinositol 3-kinase(PI3K)/Akt signaling against MPP^+-induced toxicity using neuroblastoma SH-SY5Y cells. The other types of NSAIDs did not show neuroprotection in the same assays. In a chronic mouse model of Parkinson's disease, meloxicam ameliorated motor dysfunction and dopaminergic neurodegeneration by maintaining Akt-signaling. These results suggest that meloxicam would be a candidate agent as a disease-modifying drug for Parkinson's disease.

Research Products

• [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: 北海道医学雑誌 Volume: 88(1) Pages: 45
• [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: doi:10.1016/j.neulet.2012.05.045.
• [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: doi:10.1016/j.ejphar.2011.11.046.
• [Journal Article] Meloxicam protects cell damage from 1-methyl-4-phenyl pyridinium toxicity via the phosphatidylinositol 3-kinase/Akt pathway in human dopaminergic neuroblastoma SH-SY5Y
  • Author(s): Tasaki Y, Omura T, Yamada T, Ohkubo T, Suno M, Iida S, Sakaguchi T, Asari M, Shimizu K, Matsubara K.
  • Journal Title: cells.
  • DOI: doi:10.1016/j.brainres.2010.04.085.
• [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
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-28
• [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, Onoa T., Kimura N., Suno M., T. Sakaguchi, and Matsubara K
  • Organizer: Neuroscience 2012
  • Place of Presentation: シカゴ,米国
  • Year and Date: 20121100
• [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): 田崎嘉一ら
  • Organizer: 日本薬学会第132年会
  • Place of Presentation: 札幌
  • Year and Date: 20120300
• [Presentation] オキシカム系NSAIDsによる神経細胞死抑制作用はAkt/mTOR経路を介する (2011)
  • Author(s): 田崎嘉一ら
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡
  • Year and Date: 20110300
• [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 T, Ohkubo T, Shimizu K and Matsubara K
  • Organizer: PDRD
  • Place of Presentation: 上海,中国
  • Year and Date: 20110000