Analyses for transport of Amyloid beta through the blood-brain barrier

• Project/Area Number: 23790994
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Yamaguchi University
• Principal Investigator: SANO Yasuteru 山口大学, 医学(系)研究科(研究院), 助教 (20379978)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: アミロイドβ / 血液脳関門 / アルツハイマー病 / Aβ蛋白 / Ａβ蛋白

Research Abstract

The clearance of amyloid beta (Ab) from the brain could be a novel therapeutic target for Alzheimer disease. We examined the role of efflux transporters as well as LRP1 on Ab transport on human BBB. Our results using a new human in vitro blood-brain barrier (BBB) model suggest that ABCG2 as well as LRP1 act to prevent the blood-borne Ab from entering brain at the human BBB. In addition, we also elucidated that rifampicin up-regulates the expression of LRP1 and ABCG2 in endothelial cells derived from human BBB.

Research Products

• [Journal Article] blood-neural barrier: overview and latent progress (2013)
  • Author(s): Yasuteru Sano and Takashi Kanda
  • Journal Title: Clin Exp Neuroimmunol Volume: 4 Issue: 2 Pages: 220-227
  • DOI: 10.1111/cen3.12021
  • Peer Reviewed
• [Journal Article] Establishment and characterization of spinal cord microvascular endothelial cell lines (2013)
  • Author(s): Maeda T, Sano Y, Abe M, Shimizu F, Kashiwamura Y, Ohtsuki S, Terasaki T, Obinata M, Ueda M, Kanda T
  • Journal Title: Clin Exp Neuroimmunol Volume: 4 Issue: 3 Pages: 326-338
  • DOI: 10.1111/cen3.12045
  • Peer Reviewed
• [Journal Article] NMO sera down-regulate AQP4 in human astrocyte and induce cytotoxicity independent of complement (2013)
  • Author(s): Hiroyo Haruki, Yasuteru Sano, Fumitaka Shimizu, Masatoshi Omoto, Ayako Tasaki, Mariko Oishi, Michiaki Koga, Kazuyuki Saito, Toshiyuki Takahashi, Takashi Kanda.
  • Journal Title: J Neurol Sci Volume: 331 Issue: 1-2 Pages: 136-144
  • DOI: 10.1016/j.jns.2013.05.035
  • Peer Reviewed
• [Journal Article] Blood-brain barrier destruction determines Fischer/Bickerstaff clinical phenotypes: an in vitro study (2013)
  • Author(s): Kazuyuki Saito, Fumitaka Shimizu, Michiaki Koga, Yasuteru Sano, Ayako Tasaki, Masa-aki Abe, Hiroyo Haruki, Toshihiko Maeda, S. Suzuki, Susumu Kusunoki, Hidehiro Mizusawa, Takashi Kanda.
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 84 Issue: 7 Pages: 756-765
  • DOI: 10.1136/jnnp-2012-304306
  • Peer Reviewed
• [Journal Article] Sequential changes in the non-coding control region sequences of JC polyomaviruses from the cerebrospinal fluid of patients with progressive multifocal leukoencephalopathy. (2013)
  • Author(s): Nakamichi K, Kishida S, Tanaka K, Suganuma A, Sano Y, Sano H, Kanda T, Maeda N, Kira JI, Itoh A, Kato N, Tomimoto H, Kurane I, Lim CK, Mizusawa H, Saijo M
  • Journal Title: Archives of Virology Volume: 158 Issue: 3 Pages: 639-650
  • DOI: 10.1007/s00705-012-1532-3
  • Peer Reviewed
• [Journal Article] Establishment and characterization of human peripheral nerve microvascular endothelial cell lines : a new in vitro blood-nerve barrier (BNB) model (2012)
  • Author(s): Abe M, Sano Y, Maeda T, Shimizu F, Kashiwamura Y, Haruki H, Saito K, Tasaki A, Kawai M, Terasaki T, Kanda T
  • Journal Title: Cell Struct Funct Volume: 37(2) Pages: 89-100
  • NAID: 40019581994
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22672995
  • Peer Reviewed
• [Journal Article] Stable human brain microvascular endothelial cell line retaining its barrier-specific nature independent of the passage number (2012)
  • Author(s): Sano Y, Kashiwamura Y, Abe M, Dieu LH, Huwyler J, Shimizu F, Haruki H, Maeda T, Saito K, Tasaki A and Kanda T
  • Journal Title: Clinical and Experimental Neuroimmunology Volume: 3 Issue: 1 Pages: 1-12
  • DOI: 10.1111/cen3.12001
  • Peer Reviewed
• [Journal Article] Pericyte-derived glial cell line-derived neurotrophic factor increase the expression of claudin-5 in the blood-brain barrier and the blood-nerve barrier (2012)
  • Author(s): Shimizu F, Sano Y, Saito K, Abe MA, Maeda T, Haruki H, Kanda T
  • Journal Title: Neurochem Res Volume: 37 Issue: 2 Pages: 401-409
  • DOI: 10.1007/s11064-011-0626-8
  • Peer Reviewed
• [Journal Article] Establishment and characterization of human peripheral nerve microvascular endothelial cell lines: a new in vitro blood-nerve barrier (BNB) model. (2012)
  • Author(s): Masaaki Abe
  • Journal Title: Cell Struct Funct Volume: 37 Pages: 89-100
  • Peer Reviewed
• [Journal Article] Sera from neuromyelitis optica patients disrupt the blood-brain barrier. (2012)
  • Author(s): Fumitaka Shimizu
  • Journal Title: J Neurol Neurosurg Psychiatry. Volume: 83 Pages: 288-297
  • Peer Reviewed
• [Journal Article] Isolation and properties of endothelial cells forming the blood-nerve barrier (2011)
  • Author(s): Sano Y, Kanda T
  • Journal Title: Methods Mol Biol Volume: 686 Pages: 417-25
  • DOI: 10.1007/978-1-60761-938-3_21
  • ISBN: 9781607619376, 9781607619383
  • Peer Reviewed
• [Journal Article] p.Arg332Cys mutation of NOTCH3 gene in two unrelated Japanese families with CADASIL (2011)
  • Author(s): Sano Y, Shimizu F, Kawai M, Omoto M, Negoro K, Kurokawa T, Fujisawa H, Suzuki M, Okayama N, Suehiro Y, Hinoda Y, Kanda T
  • Journal Title: Intern Med Volume: 50(22) Pages: 2833-8
  • NAID: 130001288675
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22082899
  • Peer Reviewed
• [Journal Article] Advanced glycation end-products induce basement membrane hypertrophy in endoneurial microvessels and disrupt the blood-nerve barrier by stimulating the release of TGF-β and vascular endothelial growth factor (VEGF) by pericytes (2011)
  • Author(s): Shimizu F, Sano Y, Haruki H, Kanda T
  • Journal Title: Diabetologia Volume: 54 Issue: 6 Pages: 1517-1526
  • DOI: 10.1007/s00125-011-2107-7
  • Peer Reviewed
• [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 Volume: 36 Issue: 5 Pages: 849-855
  • DOI: 10.1007/s11064-011-0413-6
  • 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 M, Maeda T, Ohtsuki S, Terasaki T, Kanda T
  • Journal Title: J Cell Physiol Volume: 226 Issue: 1 Pages: 255-266
  • DOI: 10.1002/jcp.22337
  • 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] Isolation and properties of endothelial cells forming the blood-nerve barrier. (2011)
  • Author(s): Yasuteru Sano
  • Journal Title: Methods Mol Biol. Volume: 686 Pages: 417-425
  • 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] Pericyte-derived glial cell line-derived neurotrophic factor increase the expression of claudin-5 in the blood-brain barrier and the blood-nerve barrier. (2011)
  • Author(s): Fumitaka Shimizu
  • Journal Title: Neurochem Res. Volume: 37 Pages: 401-409
  • Peer Reviewed
• [Journal Article] p.Arg332Cys mutation of NOTCH3 gene in two unrelated Japanese families with CADASIL. (2011)
  • Author(s): Yasuteru Sano
  • Journal Title: Intern Med. Volume: 50 Pages: 2833-2838
  • NAID: 130001288675
  • Peer Reviewed
• [Presentation] Role of LRP1 and ATP-binding cassette transporters in efflux of amyloid-βat the human blood-brain barrier (2013)
  • Author(s): Yasuteru Sano
  • Organizer: Neuroscience 2013
  • Place of Presentation: San Diego, USA
  • Year and Date: 2013-11-12
• [Presentation] アミロイドβ蛋白の血液脳関門を介した輸送機構の解析 (2013)
  • Author(s): 佐野泰照
  • Organizer: 第35回神経組織培養研究会
  • Place of Presentation: 吹田(ホテル阪急エキスポパーク)
• [Presentation] アミロイドβ蛋白の血液脳関門を介した輸送機構の解析～続報 (2013)
  • Author(s): 佐野泰照
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京(東京国際フォーラム)
• [Presentation] アミロイドβ蛋白の血液脳関門を介した輸送機構の解析～続報 (2013)
  • Author(s): 佐野泰照
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京（東京国際フォーラム）
• [Presentation] アミロイドβ蛋白の血液脳関門を介した輸送機構の解析 (2013)
  • Author(s): 佐野泰照
  • Organizer: 第35回神経組織培養研究会
  • Place of Presentation: 吹田，大阪（ホテル阪急エキスポパーク）
• [Presentation] Role of LRP1 and ATP-binding cassette transporters in efflux of amyloid-β at the human blood-brain barrier (2013)
  • Author(s): Yasuteru Sano
  • Organizer: Neuroscience2013
  • Place of Presentation: San Diego, USA
• [Presentation] アミロイドβ蛋白の血液脳関門を介した輸送機構の解析～第二報 (2012)
  • Author(s): 佐野泰照
  • Organizer: 第53回日本神経学会総会
  • Place of Presentation: 東京(東京国際フォーラム)
• [Presentation] アミロイドβ蛋白の血液脳関門を介した輸送機構の解析～第二報 (2012)
  • Author(s): 佐野泰照
  • Organizer: 第53回日本神経学会総会
  • Place of Presentation: 東京(東京国際フォーラム）
• [Presentation] アミロイドβ蛋白の血液脳関門を介した輸送機構の解析 (2011)
  • Author(s): 佐野泰照
  • Organizer: 第52回日本神経学会総会
  • Place of Presentation: 名古屋(名古屋国際会議場)
  • Year and Date: 2011-05-19
• [Presentation] アミロイドβ蛋白の血液脳関門を介した輸送機構の解析 (2011)
  • Author(s): 佐野泰照
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 名古屋国際会議場（名古屋）
• [Book] 最新アプローチ多発性硬化症と視神経脊髄 (2012)
  • Author(s): 佐野泰照, 他
  • Total Pages: 410
  • Publisher: 中山書店
• [Book] 最新アプローチ 多発性硬化症と視神経脊髄炎 (2012)
  • Author(s): 佐野泰照他
  • Total Pages: 410
  • Publisher: 中山書店