Studies on the role(s) of renin-angiotensin system in the pathogenesis of Alzheimer disease

2011 Fiscal Year Final Research Report

• Project/Area Number: 21300145
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: National Center for Geriatrics and Gerontology
• Principal Investigator: MICHIKAWA Makoto 独立行政法人国立長寿医療研究センター, アルツハイマー病研究部, 部長 (40270912)
• Project Period (FY): 2009 – 2011
• Keywords: 精神・神経疾患の病態と治療 / アルツハイマー病 / 蛋白分解酵素 / 治療

Research Abstract

We found that angiotensin-converting enzyme(ACE) converts Aβ42 to Aβ40 and that angiotensin II receptor mediates metabolism of Alzheimer disease-related molecules. This study was designed to clarify the involvement of renin-angiotensin system in the pathogenesis of Alzheimer disease.

Research Products

• [Journal Article] Heparan Sulfate Subdomains that are Degraded by Sulf Accumulate in Cerebral Amyloid s Plaques of Alzheimer's Disease : Evidence from Mouse Models and Patients (2012)
  • Author(s): Hosono-Fukao T, Ohtake-Niimi S, Hoshino H, Akatsu H, Hossain M, Nishitsuji K, van Kuppevelt, Kimata K, Michikawa M, Wyss-Coray T, Uchimura K.
  • Journal Title: Am J Pathol Volume: 180(5) Pages: 2056-2067
• [Journal Article] Lipoprotein lipase is a novel Aβ-binding protein that promotes glycosaminoglycan-dependent cellular uptake of Aβin astrocytes (2011)
  • Author(s): Nishitsuji K, Hosono T, Uchimura K, Michikawa M.
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 6393-6401
• [Journal Article] Apolipoprotein E regulates the integrity of tight junctions in an isoform-dependent manner in an in vitro blood-brain-barrier model (2011)
  • Author(s): Nishitsuji K, Hosono T, Nakamura T, Bu G, Michikawa M.
  • Journal Title: Biol. Chem Volume: 286(20) Pages: 17536-17542
• [Journal Article] The dissociation of Aβfrom lipoprotein in cerebrospinal fluid from Alzheimer's disease accelerates Aβ42 assembly (2011)
  • Author(s): Takamura A, Kawarabayashi T, Yokoseki T, Shibata M, Morishima-Kawashima M, Saito Y, Murayama S, Ihara Y, Abe K, Shoji M, Michikawa M, Matsubara E.
  • Journal Title: J. Neurosci. Res Volume: 6 Pages: 815-821
• [Journal Article] Extracellular and intraneuronal HMW-Aβoligomers represent a molecular basis of memory loss in Alzheimer's disease model mouse (2011)
  • Author(s): Takamura A, Okamoto Y, Kawarabayashi T, Yokoseki T, Shibata M, Mouri A, Nabeshima T, Sun H, Abe K, Shoji M, Yanagisawa K, Michikawa M, Matsubara E.
  • Journal Title: Mol. Neurodegener Volume: 6 Pages: 20
• [Journal Article] Higher activity of peripheral blood angiotensin-converting enzyme is associated with later-onset of Alzheimer's disease. (2011)
  • Author(s): Akatsu H, Ogawa N, Kanesaka T, Hori A, Yamamoto T, Matsukawa N, Michikawa M.
  • Journal Title: J. Neurol. Sci Volume: 300 Pages: 67-73
• [Journal Article] ER-stress-inducible Herp, facilitates the degradation f immature nicastrin (2011)
  • Author(s): Marutani T, Maeda T, Tanabe C, Zou K, Araki W, Kokame K, Michikawa M, Komano H.
  • Journal Title: Biochim. Biophys. Acta Volume: 1810 Pages: 790-8
• [Journal Article] RB4CD12 epitope expression and heparan sulfate disaccharide composition in brain vasculature. (2011)
  • Author(s): Hosono-Fukao T, Ohtake-Niimi S, Nishitsuji K, Hossain M, van Kuppevelt TH, Michikawa M, Uchimura K.
  • Journal Title: J. Neurosci. Res Volume: 89 Pages: 1840-8
• [Journal Article] Beta-amyloid increases the expression level of ATBF1 responsible for death in cultured cortical neurons (2011)
  • Author(s): Jung C-G, Uhm K-O, Miura Y, Hosono T, Horike H, Khanna K K, Michikawa M.
  • Journal Title: Mol Neurodegener Volume: 6 Pages: 47
• [Journal Article] Homocysteine, another risk factor for Alzheimer's disease, impairs apolipoprotein E3 function (2010)
  • Author(s): Minagawa H, Watanabe A, Akatsu H, Adachi K, Ohtsuka C, Terayama Y, Hosono T, Takahashi S, Wakita H, Jung C-G, Komano H, Michikawa M.
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 38382-38388
• [Journal Article] Honokiol increases ABCA1 expression level by activating retinoid X receptorβ (2010)
  • Author(s): Jung C-G, Horike H, Cha B-Y, Uhm K-O, Yamauchi R, Yamaguchi T, Hosono T, Iida K, Woo J-T, Michikawa M
  • Journal Title: Biol. Pharm. Bull Volume: 33 Pages: 1105-1111
• [Journal Article] Apolipoprotein E4(1-272) fragment is associated with mitochondrial proteins and affects mitochondrial function in neuronal cells (2009)
  • Author(s): Nakamura T, Watanabe A, Fujino T, Hosono T, and Michikawa M
  • Journal Title: Mol. Neurodegener Volume: 4 Pages: 35
• [Journal Article] Microglia activated with toll-like receptor 9 ligand CpG attenuate oligomeric amyloid-βneurotoxicity in vitro and in vivo models of Alzheimer's disease (2009)
  • Author(s): Doi Y, Mizuno T, Maki Y, Jin S, Mizoguchi H, Ikeyama M, Doi M, Michikawa M, Takeuchi H, and Suzumura A.
  • Journal Title: Am. J. Pathol Volume: 175 Pages: 2121-2132
• [Journal Article] An E3 ubiquitin ligase, synoviolin is involved in the degradation of immature nicastrin, and regulates the production of amyloidβ-protein (2009)
  • Author(s): Maeda T, Marutani T, Zou K, Araki W, Yagishita N, Yamamoto Y, Amano T, Michikawa M, Nakajima T, and Komano H.
  • Journal Title: FEBS J Volume: 276 Pages: 5832-5840
• [Journal Article] Aβ42-to-Aβ40-and angiotensin-converting activities in different domain of angiotensin-converting enzyme (2009)
  • Author(s): Zou K, Maeda T, Oba R, Komano H, and Michikawa M
  • Journal Title: Biol. Chem Volume: 284 Pages: 31914-31920
• [Journal Article] Bioactive TGF-βcan associate with lipoproteins and is enriched in those containing apolipoprotein E3 (2009)
  • Author(s): Tesseur I, Brecht W, Corn J, Gong J-S, Yanagisawa K, Michikawa M, Weisgraber K, Huang Y, and Wyss-Coray T.
  • Journal Title: J. Neurochem Volume: 110(4) Pages: 1254-1262
• [Journal Article] Mechanism underlying apolipoprotein E isoform-dependent lipid efflux from neural cells in culture (2009)
  • Author(s): Minagawa H, Gong J-S, Jung C-G, Watanabe A, Lund-Katz S, Phillips M C, Saito H, Michikawa M.
  • Journal Title: J. Neurosci. Res Volume: 87 Pages: 2498-2508
• [Journal Article] Association between cognitive function and plasma lipids of the elderly after controlling for apolipoprotein E genotype
  • Author(s): Yasuno F, Tanimukai S, Sasaki M, Hidaka S, Ikejima C, Yamashita F, Kodama C, Mizukami K, Michikawa M, Asada T.
  • Journal Title: Am. J. Geriat. Psychiat Volume: (in press)
• [Presentation] 脳内脂質代謝変動とアルツハイマー病分子病態 (2011)
  • Author(s): 道川誠
  • Organizer: 第5回関西・中部認知症学会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-02-19
• [Presentation] アポリポ蛋白Eとアルツハイマー病 (2010)
  • Author(s): 道川誠
  • Organizer: 教育講演:第18回中部老年期認知症研究会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-10-30
• [Presentation] Apolipoprotein E and Alzheimer's Disease (2010)
  • Author(s): 道川誠
  • Organizer: 中国瀋陽医学院・何氏視覚科学学院
  • Place of Presentation: 瀋陽、中国
  • Year and Date: 2010-09-27
• [Presentation] 炎症とアルツハイマー病 (2010)
  • Author(s): 道川誠
  • Organizer: 日本歯周病学会シンポジウム
  • Place of Presentation: 高松
  • Year and Date: 2010-09-19
• [Presentation] Potent inhibition of ACE leads to Alzheimer-like pathology in APP transgenic mouse brain (2010)
  • Author(s): Zou K, Liu S, Liu J, Tanabe C, Maeda T, Michikawa M, Komano H.
  • Organizer: International Conference on Alzheimer's Disease(ICAD)
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 2010-07-11
• [Presentation] TBF1 interacts with amyloid precursor protein and enhances amyloid b production (2010)
  • Author(s): Uhm KO, Horike H, Michikawa M, Jung CG
  • Organizer: International Conference on Alzheimer's Disease(ICAD)
  • Place of Presentation: Honolulu, Hawaii
  • Year and Date: 2010-07-11
• [Presentation] ATBF1 interacts with amyloid precusor protein and enhances amyloidβ-protein production (2010)
  • Author(s): Uhm KO, Horike H, Miura Y, Akatsu H, Michikawa M, Jung CG.
  • Organizer: The First International Conference on Neural Cell Culture(ICNCC 2010)
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2010-06-25
• [Presentation] Apolipioprotein E and Alzheimer's disease Hallym University (2010)
  • Author(s): Michikawa M.
  • Organizer: The 12th Ilsong International Symposium, Hallym-Nagoya Academic Joint Meeting
  • Place of Presentation: Hallym University, Gyeonggi-do, Korea
  • Year and Date: 2010-06-24
• [Presentation] アルツハイマー病とスタチン脳を護るー認知症を防ぐー興和創薬 (2010)
  • Author(s): 道川誠
  • Organizer: 名古屋医師会共催シンポジウム
  • Place of Presentation: 名古屋
  • Year and Date: 2010-06-17
• [Presentation] Effect of apolipoprotein E isofrom on formation and maintenance of blood-brain-barrier function (2010)
  • Author(s): Kazuchika N, Hosono T, Nakamura T, and Michikawa M.
  • Organizer: Washington University, St
  • Place of Presentation: Louis, USA
  • Year and Date: 2010-06-07
• [Presentation] レニンアギオテシ系とアルツハイマー病 (2010)
  • Author(s): 道川誠
  • Organizer: 慈恵医大神経疾患研究会
  • Place of Presentation: 東京
  • Year and Date: 2010-02-18
• [Presentation] Mechanism underlying apolipoprotein E(ApoE) isoform-dependent HDL generation and impairment of ApoE3-mediated HDL generation by homocysteine (2009)
  • Author(s): Minagawa K, Gong J-S, Akatsu H. Jung C-G, Watanabe A, Nishitsuji K, Hosono T, Lund-Katz S, Phillips M C, Komano H, Saito H, and Michikawa M
  • Organizer: International conference on Alzheimer's disease(ICAD)
  • Place of Presentation: Vienna, Austria
  • Year and Date: 20090612-16
• [Presentation] Ab42-toAb40-and angiotensin-converting activities in different domains of angiotensin-converting enzyme (2009)
  • Author(s): Zou K, Maeda T, Oba R, Michikawa M, Komano H.
  • Organizer: International conference on Alzheimer's disease(ICAD)
  • Place of Presentation: Vienna, Austria
  • Year and Date: 20090612-16
• [Presentation] Low activity of angiotensin-converting enzyme(ACE) is a risk factor for onset of Alzheimer's disease (2009)
  • Author(s): Akatsu H, Matsuyama Z, Matsukawa N, Hori A, Yamamoto T, Michikawa M
  • Organizer: International conference on Alzheimer's disease(ICAD)
  • Place of Presentation: Vienna, Austria
  • Year and Date: 20090612-16
• [Presentation] Aβenhances the ATBF1 expression responsible for the neuronal cell death (2009)
  • Author(s): Jung CG, Kawaguchi M, Miura Y, Akatsu H, Hosono T, Uhm KO, Michikawa M.
  • Organizer: International conference on Alzheimer's disease(ICAD)
  • Place of Presentation: Vienna, Austria
  • Year and Date: 20090612-16
• [Presentation] レニンアンギオテンシン系とアミロイドベータ蛋白代謝 (2009)
  • Author(s): 道川誠
  • Organizer: 第28回日本認知症学会シンポジウム
  • Place of Presentation: 東北大学百周年記念会館,仙台
  • Year and Date: 2009-11-21
• [Presentation] The role of ATBF1 in Alzheimer's disease (2009)
  • Author(s): Jung CG, Kawaguchi M, Miura Y, Akatsu H, Hosono T, Uhm KO, Michikawa M.
  • Organizer: International Society for Neurochemistry(ISN)/Asia-Pacific Society for Neurochemistry(APSN)
  • Place of Presentation: Busan, Korea
  • Year and Date: 2009-08-24
• [Presentation] Apolipoprotein E(1-272) fragment is associated with mitochondrial proteins and affects mitochondrial function in neuronal cells (2009)
  • Author(s): Michikawa M, Nakamura T, Watanabe A, Hosono T, Fujino T.
  • Organizer: International Society for Neurochemistry(ISN)/Asia-Pacific Society for Neurochemistry(APSN)
  • Place of Presentation: Busan, Korea
  • Year and Date: 2009-08-24
• [Presentation] The cholesterol paradox in the pathogenesis of Alzheimer's disease (2009)
  • Author(s): 道川誠
  • Organizer: 第51回日本脂質生化学会
  • Place of Presentation: 名古屋
  • Year and Date: 2009-07-30
• [Presentation] 脳内脂質代謝の生理学的ならびに病理学的意義について (2009)
  • Author(s): 道川誠
  • Organizer: 日本膜学会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2009-05-22
• [Book] コレステロール代謝とアルツハイマー病 (2009)
  • Author(s): 道川誠
  • Total Pages: 129-136
  • Publisher: シーエムシー出版
• [Patent(Industrial Property Rights)] アルツハイマー病の予防及び治療薬並びにアルツハイマー病の予防及び治療薬のスクリーニング方法 (2009)
  • Inventor(s): 道川誠、西辻和親
  • Industrial Property Rights Holder: 財団法人ヒューマンサイエンス振興財団
  • Industrial Property Number: 2009-289487
  • Filing Date: 2009-12-21