The analysis of the transportation of amyloid-β peptide across the blood-brain barrier

• Project/Area Number: 21790841
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: Yamaguchi University
• Principal Investigator: SANO Yasuteru Yamaguchi University, 医学部附属病院, 助教 (20379978)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: アルツハイマー病 / 血液脳関門 / Aβ蛋白 / ABCG2 / アミロイド蛋白

Research Abstract

Alzheimer's disease (AD) is the most common cause of dementia. Although several in vivo studies suggest that the blood-brain barrier is compromised in AD brain, the underlying mechanisms remain unclear. In this study, we demonstrated that Aβ42 decreased the expression of claudin-5 and disrupted the tight junction of human brain endothelial cell lines. In addition, we examined whether efflux transporters expressed in the BBB are involved in the transportation of Aβ across the BBB. Our in vitro study suggested that ABCG2 transcytosed Aβ40 out of the brain across the blood-brain barrier.

Research Products

• [Journal Article] Hydrocortisone enhances the function of the blood-nerve barrier through the up-regulation of claudin-5 (2011)
  • Author(s): Kashiwamura Y, Sano Y, Abe M, Shimizu F, Haruki H, Maeda T, Kawai M, Kanda T.
  • Journal Title: Neurochem Res. 36 Pages: 849-855
  • Peer Reviewed
• [Journal Article] Peripheral nerve pericytes modify the blood-nerve barrier function and tight junctional molecules through the secretion of various soluble factors. (2011)
  • Author(s): Shimizu F, Sano Y, Abe MA, Maeda T, Ohtsuki S, Terasaki T, Kanda T.
  • Journal Title: J Cell Physiol. 226 Pages: 255-266
  • Peer Reviewed
• [Journal Article] Peripheral nerve pericytes modify the blood-nerve barrier function and tight junctional molecules through the secretion of various soluble factors. (2011)
  • Author(s): Fumitaka Shimizu
  • Journal Title: J Cell Physiol Volume: 226 Pages: 255-266
  • Peer Reviewed
• [Journal Article] Hydrocortisone enhances the function of the blood-nerve barrier through the up-regulation of claudin-5. (2011)
  • Author(s): Yoko Kashiwamura
  • Journal Title: Neurochem Res Volume: 36 Pages: 849-855
  • Peer Reviewed
• [Journal Article] Establishment of a new conditionally immortalized human brain microvascular endothelial cell line retaining an in vivo blood-brain barrier function. (2010)
  • Author(s): Sano Y, Shimizu F, Abe M, Maeda T, Kashiwamura Y, Ohtsuki S, Terasaki T, Obinata M, Kajiwara K, Fujii M, Suzuki M, Kanda T.
  • Journal Title: J Cell Physiol. 225 Pages: 519-528
  • Peer Reviewed
• [Journal Article] Establishment of a new conditionally immortalized human brain microvascular endothelial cell line retaining an in vivo blood-brain barrier function (2010)
  • Author(s): Yasuteru Sano
  • Journal Title: J Cell Physiol Volume: 225 Pages: 519-528
  • Peer Reviewed
• [Journal Article] Interleukin-25 expressed by brain capillary endothelial cells maintains blood-brain barrier function in a protein kinase Cepsilon-dependent manner. (2009)
  • Author(s): Sonobe Y, Takeuchi H, Kataoka K, Li H, Jin S, Mimuro M, Hashizume Y, Sano Y, Kanda T, Mizuno T, Suzumura A.
  • Journal Title: J Biol Chem. 284 Pages: 31834-31842
  • Peer Reviewed
• [Journal Article] Interleukin-25 expressed by brain capillary endothelial cells maintains blood-brain barrier function in a protein kinase Cepsilon-dependent manner. (2009)
  • Author(s): Yoshifumi Sonobe
  • Journal Title: The Journal of the biological chemistry 284 Pages: 31834-31842
  • Peer Reviewed
• [Presentation] Aβ42 species disrupt the blood-brain barrier through the down-regulation of claudin-5 (2010)
  • Author(s): Yasuteru Sano, Takashi Kanda
  • Organizer: Neuroscience 2010
  • Place of Presentation: San Diego, USA.
  • Year and Date: 2010-11-13
• [Presentation] Establishment of glio-vascular unit model to reveal of pathogenesis of neuromyelitis optica. (2010)
  • Author(s): Hiroyo Haruki, Yasuteru Sano, Fumitaka Shimizu, Tsutomu Nakata, Takashi Kanda.
  • Organizer: Neuroimmunology Kyoto Conference 2010.
  • Place of Presentation: 京都,京都ガーデンパレス
  • Year and Date: 2010-08-21
• [Presentation] Establishment of a new conditionally immortalized human brain microvascular endothelial cell line retaining an in vivo blood-brain barrier function. (2010)
  • Author(s): Yasuteru Sano, Fumitaka Shimizu, Hiroyo Haruki, Kazuyuki Saito, Takashi Kanda
  • Organizer: The First International Conference on Neural Tissue Culture.
  • Place of Presentation: Seoul, Korea.
  • Year and Date: 2010-06-25
• [Presentation] アミロイドβ蛋白のヒト脳微小血管内皮細胞のtight junctionへの影響 (2010)
  • Author(s): 佐野泰照
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京 東京國際フォーラム
  • Year and Date: 2010-05-22
• [Presentation] アミロイドβ蛋白のヒト脳微小血管内皮細胞のtight junctionへの影響 (2010)
  • Author(s): 佐野泰照, 清水文崇, 柏村陽子, 春木明代, 神田隆
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京,東京国際フォーラム
  • Year and Date: 2010-05-21
• [Presentation] Neuromyelitis optica (NMO)患者血清が血液脳関門(BBB)に及ぼす影響の解析 (2010)
  • Author(s): 清水文崇, 佐野泰照, 藤澤美和子, 柏村陽子, 春木明代, 神田隆
  • Organizer: 第22回日本神経免疫学会学術集会
  • Place of Presentation: 東京,日経ホール
  • Year and Date: 2010-03-18
• [Presentation] Effect of amyloid β on tight junction of the new conditionally immortalized human brain microvascular endothelial cell line (2009)
  • Author(s): Yasuteru Sano
  • Organizer: Neuroscience2009
  • Place of Presentation: Chicago, USA.
  • Year and Date: 2009-10-21
• [Presentation] Effect of amyloid β on tight junction of the new conditionally immortalized human brain microvascular endothelial cell line (2009)
  • Author(s): Yasuteru Sano
  • Organizer: Neuroscience2009
  • Place of Presentation: Chicago, USA
  • Year and Date: 2009-10-21
• [Presentation] The effect of IFN-β1b on the human in vitro blood-brain barrier model (2009)
  • Author(s): Yasuteru Sano
  • Organizer: 第8回脳血管国際会議
  • Place of Presentation: 仙台,仙台エクセルホテル東急
  • Year and Date: 2009-06-29
• [Presentation] The effect of IFN-β1b on the human in vitro blood-brain barrier model (2009)
  • Author(s): Yasuteru Sano
  • Organizer: 第8回脳血管国際会議
  • Place of Presentation: 仙台
  • Year and Date: 2009-06-29
• [Presentation] 血液脳関門のバリア機能を増強させうる薬物の作用機序の検討 (2009)
  • Author(s): 佐野泰照, 前田敏彦, 柏村陽子, 安部真彰, 清水文崇, 鈴木倫保, 神田隆
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台,仙台国際センター
  • Year and Date: 2009-05-21
• [Presentation] 血液脳関門のバリア機能を増強させうる薬物の同定およびそのメカニズムの検討 (2009)
  • Author(s): 佐野泰照, 柏村陽子, 前田敏彦, 安部真彰, 清水文崇, 鈴木倫保, 寺崎哲也, 神田隆
  • Organizer: 第21回日本神経免疫学会学術集会
  • Place of Presentation: 大阪,大阪国際会議場
  • Year and Date: 2009-03-12
• [Remarks] ホームページ等