Berberine, a candidate drug to control the development of Alzheimer's disease

• Project/Area Number: 20590260
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Saitama Medical University
• Principal Investigator: MARUYAMA Kei Saitama Medical University, 医学部, 教授 (30211577)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: アルツハイマー病 / アミロイド / 認可薬剤 / ベルベリン / 併用療法 / セクレターゼ / ネプリライシン / 神経防護 / βアミロイド / 神経防護作用 / 認可薬物 / 多剤併用療法 / 臨床使用 / 安全性

Research Abstract

The substances for the treatment of Alzheimer's disease, which decreased Aβ levels, were screened from clinically approved drugs. We identified KM2309 (code name, because of patent application). It inhibited γ-secretase and up-regulated a major Aβ-degrading enzyme neprilysin. Since it has been reported that KM2309 crosses the BBB and it has neuronal protective effect, KM2309 would be a novel drug candidate with safety for Alzheimer's disease.

Research Products

• [Journal Article] Stimulation of Non-Amyloidogenic Processing of Amyloid-β Protein Precursor by Cryptotanshinone Involves Activation and Translocation of ADAM10 and PKC-α (2011)
  • Author(s): Durairajan SS, et al.
  • Journal Title: J Alzheimers Dis Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Non-activated APJ suppresses the angiotensin II type 1 receptor, whereas apelin-activated APJ acts conversely (2011)
  • Author(s): Sun X, et al.
  • Journal Title: Hypertens Res Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Efficient four-drug cocktail therapy targeting amyloid-β peptide for Alzheimer's disease (2010)
  • Author(s): Asai M, Iwata N, Tomita T, Iwatsubo T, Ishiura S, Saido TC, Maruyama K
  • Journal Title: J Neurosci Res 88 Pages: 3588-3597
  • Peer Reviewed
• [Journal Article] Efficient four-drug cocktail therapy targeting amyloid-β peptide for Alzheimer's disease (2010)
  • Author(s): Asai M, et al.
  • Journal Title: J Neurosci Res Volume: 30 Pages: 3588-3597
  • Peer Reviewed
• [Journal Article] Distinct roles of the DRY motif in rat melanin-concentrating hormone receptor 1 in signaling control (2009)
  • Author(s): Aizaki Y, Maruyama K, Nakano-Tetsuka M, Saito Y
  • Journal Title: Peptides 30 Pages: 974-981
  • NAID: 120001107860
  • Peer Reviewed
• [Journal Article] Distinct roles of the DRY motif in rat melanin-concentrating hormone receptor 1 in signaling control (2009)
  • Author(s): Aizaki Y
  • Journal Title: Peptides 30 Pages: 974-981
  • Peer Reviewed
• [Journal Article] Regulation of melanin-concentrating hormone receptor I signaling by RGS8 with the receptor third intracellular loop. (2008)
  • Author(s): Miyamoto-Matsubara M.
  • Journal Title: Cellular Signaling 20 Pages: 2084-2094
  • Peer Reviewed
• [Journal Article] Senbonmatsu T, Non-activated APJ suppresses the angiotensin II type 1 receptor, whereas apelin-activated APJ acts conversely
  • Author(s): Sun X, Iida S, Yoshikawa A, Senbonmatsu R, Imanaka K, Maruyama K, Nishimura S, Inagami T
  • Journal Title: Hypertens Res in press
  • Peer Reviewed
• [Journal Article] Stimulation of Non-Amyloidogenic Processing of Amyloid-β Protein Precursor by Cryptotanshinone Involves Activation and Translocation of ADAM10 and PKC-α
  • Author(s): Durairajan SS, Liu LF, Lu JH, Koo I, Maruyama K, Chung SK, Huang JD, Li M
  • Journal Title: J Alzheimers Dis in press
  • Peer Reviewed
• [Presentation] 認可薬剤KM2309 のAPP 代謝およびAβ分解に対する影響 (2011)
  • Author(s): 浅井将、丸山敬, 等
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: (震災によりWeb会議)
• [Presentation] 臨床使用されている薬物KM2309 のAPP 代謝およびAβ分解に対する影響 (2010)
  • Author(s): 浅井将、丸山敬, 等
  • Organizer: BMB2010(第33回日本分子生物学会年会・第83回日本生化学会大会合同大会)
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] 臨床使用されている薬物KM2309 のAPP 代謝およびAβ分解に対する影響 (2010)
  • Author(s): 浅井将、丸山敬, 等
  • Organizer: 第29回日本認知症学会学術集会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-11-05
• [Presentation] YセクレターゼとカテプシンBによるAPPC末端断片の代謝制御 (2010)
  • Author(s): 浅井将
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-16
• [Presentation] カテプシンB 阻害剤CA-074Me はAPP C 末端断片の蓄積をもたらす (2009)
  • Author(s): 浅井将、丸山敬, 等
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-21
• [Presentation] Cathepsin B によるAPPC 末端断片の代謝制御 (2009)
  • Author(s): 浅井将、丸山敬, 等
  • Organizer: 第14回日本病態プロテアーゼ学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-08-21
• [Presentation] Cathepsin B inhibitor CA-074Me causes the alteration of APP catabolism independently of secretase activities. (2008)
  • Author(s): 浅井将、丸山敬, 等, et al.
  • Organizer: 11th International Symposium on Proteinase Inhibitors and Biological Control, Portoro? (Slovenia)
  • Place of Presentation: スロベニア
  • Year and Date: 2008-08-30
• [Presentation] Cathepsin B inhibitor CA-074Me causes the alteration of APP catabolism independently of secretase activities (2008)
  • Author(s): Asai, M.
  • Organizer: 11th International Symposium on Proteinase Inhibitors and Biological Control
  • Place of Presentation: Portoroz (スロベニア)
• [Presentation] 認可薬剤KM2309のAPP代謝およびAβ分解に対する影響
  • Author(s): 浅井将
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: (紙上発表)
• [Book] カラー図解アメリカ版大学生物学の教科書(細胞生物学) (2010)
  • Author(s): 石崎泰樹,丸山敬(編集,翻訳)
  • Total Pages: 318
  • Publisher: 講談社
• [Book] カラー図解アメリカ版大学生物学の教科書(分子遺伝学) (2010)
  • Author(s): 石崎泰樹,丸山敬(編集,翻訳)
  • Total Pages: 422
  • Publisher: 講談社
• [Book] カラー図解アメリカ版大学生物学の教科書(分子生物学) (2010)
  • Author(s): 石崎泰樹,丸山敬(編集,翻訳)
  • Total Pages: 402
  • Publisher: 講談社
• [Book] MR 薬理学 (2010)
  • Author(s): 遠藤實(監修), 丸山敬, 淡路健雄(編集)
  • Total Pages: 286
  • Publisher: 恒心社出版
• [Book] カラー図解アメリカ版大学生物学の教科書(分子遺伝学) (2010)
  • Author(s): 丸山敬, ら
  • Total Pages: 424
  • Publisher: 講談社
• [Book] 私が何を忘れたか、思い出せない (2009)
  • Author(s): 丸山敬(監訳), 田中敦子(訳)
  • Total Pages: 361
  • Publisher: ウェッジ
• [Book] 実技試験攻略のための基本的臨床技能 (2009)
  • Author(s): 丸山敬
  • Publisher: 丸善
• [Book] カッツング薬理学 (2009)
  • Author(s): 丸山敬, その他(編集・翻訳)
  • Total Pages: 1237
  • Publisher: 丸善
• [Book] イラストレイテッド生化学原書4版 (2008)
  • Author(s): 丸山敬, 他(編集・翻訳)
  • Total Pages: 619
  • Publisher: 丸善
• [Book] アルツハイマー病up to date (2008)
  • Author(s): 丸山敬(編集)
  • Total Pages: 40
  • Publisher: ニューサイエンス社
• [Remarks] ホームページ等
  • URL: http://www.saitama-med.ac.jp/uinfo/yakuri/index.html