New Therapeutical Approach for Neural Disorders Focusing on Angiotensin II type 2 Receptor Signaling

• Project/Area Number: 19791000
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Cerebral neurosurgery
• Research Institution: Ehime University
• Principal Investigator: MOGI Masaki Ehime University, 大学院・医学系研究科, 講師 (20363236)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,000,000 (Direct Cost: ¥2,000,000)
• Keywords: レニンアンジオテンシン系 / 脳梗塞 / 認知機能障害 / メタボリックシンドローム / 血管老化 / アンジオテンシンII2型受容体 / アンジオテンシンII受容体ブロッカー / 細胞治療 / 虚血再環流障害 / 骨髄ストローマ細胞 / 炎症 / 脳浮腫 / レニン・アンジオテンシン系 / 多発性硬化症 / 神経保護療法

Research Abstract

脳卒中やアルツハイマー病などの神経疾患はこれからの超高齢化社会において克服するべき重要な病気ですが有効な治療法は確立されていません。最近高血圧調節ホルモンであるレニン・アンジオテンシン系を調節する降圧薬(ARB)の効果が注目されており、我々は本研究において、脳梗塞や認知機能に焦点を当てたマウスを用いた動物実験により、ARBが神経細胞の障害を抑制したり、血管細胞の老化を防いだり、脳梗塞後の生存率を上げるような治療が可能になることを見出しました。

Research Products

• [Journal Article] Reduced angiotensin II levels in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis (2009)
  • Author(s): Kawajiri M., M. Mogi, JI. Kira et al
  • Journal Title: Acta Neurol Scand 119 Pages: 341-344
  • Peer Reviewed
• [Journal Article] Angiotensin-converting enzyme (ACE) and ACE2 levels in the cerebrospinal fluid of patients with multiple sclerosis (2009)
  • Author(s): Kawajiri M., M. Mogi, JI. Kira et al
  • Journal Title: Mult Scler 15 Pages: 262-265
  • Peer Reviewed
• [Journal Article] Reduced angiotensin II levels in the cerebrospinal fluid of patients with anryalrephic lateral sde sis (2009)
  • Author(s): Kawajiri M Mogi M., et.al.
  • Journal Title: Acta Neurol Scand (in press)
  • Peer Reviewed
• [Journal Article] Telmisartan prevented cognitive decline partly due to PPAR-gamma activation (2008)
  • Author(s): Mogi M, JM Li, M Horiuchi et al
  • Journal Title: Biochem Biophys Res Commun 375 Pages: 446-449
  • Peer Reviewed
• [Journal Article] New insight of angiotensin II receptor blocker treatment in cardiac dysfunction using angiotensin-converting enzyme 2-deficient mice (2008)
  • Author(s): Mogi M, M. Horiuchi
  • Journal Title: Hypertens Res 31 Pages: 1833-4
  • NAID: 10024827315
  • Peer Reviewed
• [Journal Article] Akt-FOXO3a signaling affects human endothelial progenitor cell differentiation (2008)
  • Author(s): Mogi M., K. Walsh, M. Iwai, and M. Horiuchi
  • Journal Title: Hypertens Res 31 Pages: 153-159
  • NAID: 10021261462
  • Peer Reviewed
• [Journal Article] Reduction of angiotensin II in the cerebrospinal fluid of patients with multiple sclerosis (2008)
  • Author(s): Kawajiri M., M. Mogi, JI. Kira et al
  • Journal Title: Mult Scler 14 Pages: 557-560
  • Peer Reviewed
• [Journal Article] Deletion of angiotensin II type 2 receptor attenuates protective effects of bone marrow stromal cell treatment on ischemia reperfusion brain injury in mice (2008)
  • Author(s): Iwanami J., M. Mogi, M. Horiuchi et al
  • Journal Title: Stroke 39 Pages: 2554-2559
  • Peer Reviewed
• [Journal Article] Temporary pretreatment with angiotensin II type 1 receptor blocker, valsartan, prevents ischemic brain damage via increase in capillary density (2008)
  • Author(s): Li J.M., M. Mogi, M. Horiuchi et al
  • Journal Title: Stroke 39 Pages: 2029-2036
  • Peer Reviewed
• [Journal Article] Angiotensin II type 2 receptor deletion enhances vascular senescence by methyl methanesulfonate sensitive 2 inhibition (2008)
  • Author(s): Min L. J., M. Mogi, M. Horiuchi et al
  • Journal Title: Hypertension 51 Pages: 1339-1344
  • Peer Reviewed
• [Journal Article] Diabetes-associated cognitive impairment is improved by a calcium channel blocker, nifedipine (2008)
  • Author(s): Tsukuda K., M. Mogi, M. Horiuchi et al
  • Journal Title: Hypertension 51 Pages: 528-533
  • Peer Reviewed
• [Journal Article] Blockade of AT1 receptor improves adipocyte differentiation in atherosclerotic and diabetic models (2008)
  • Author(s): Tomono Y., M. Mogi, M. Horiuchi
  • Journal Title: Am J Hypertens 21 Pages: 206-212
  • Peer Reviewed
• [Journal Article] Attenuation of focal brain ischemia by telmisartan, an angiotensin II type 1 receptor blocker, in atherosclerotic apolipoprotein E-deficient mice (2008)
  • Author(s): Iwai M., M. Mogi, M. Horiuchi et al
  • Journal Title: Hypertens Res 31 Pages: 161-168
  • NAID: 10021261491
  • Peer Reviewed
• [Journal Article] アルドステロンと脳血管障害 (2008)
  • Author(s): 茂木正樹、岩波純、堀内正嗣
  • Journal Title: Mebio 25 Pages: 54-61
• [Journal Article] ARBと脳卒中 (2008)
  • Author(s): 茂木正樹、堀内正嗣
  • Journal Title: 分子心血管病 9 Pages: 29-34
• [Journal Article] Deletion of angiotensin II type 2 receptor attenuates protective effects of bone marrow stromal cell treatment on ischemia-reperfusion brain injury in mice (2008)
  • Author(s): Iwanami J., Mogi M., et.al.
  • Journal Title: Stroke 39 Pages: 2554-2559
  • Peer Reviewed
• [Journal Article] Telmisartan prevented cognitive decline partly due to PPAR-gamma activation (2008)
  • Author(s): Mogi M., Horiuchi M., et.al.
  • Journal Title: Biochem Biophys Res Commun 375 Pages: 6-9
  • Peer Reviewed
• [Journal Article] Temporary pretreatment with the angiotensin II type 1 receptor blocker, valsartan, prevents ischemic brain damage through an increase in capillary density (2008)
  • Author(s): Li JM., Mogi M., et.al.
  • Journal Title: Stroke 39 Pages: 2029-2036
  • Peer Reviewed
• [Journal Article] Angiotensin II type 2 receptor deletion enhances vascular senescence by methyl methanesulfonate sensitive 2 inhibition. (2008)
  • Author(s): Min LJ., Mogi M., et.al.
  • Journal Title: Hypertension 51 Pages: 1339-1344
  • Peer Reviewed
• [Journal Article] Angiotensin II Type 2 Receptor Deletion Enhances Vasoular Senescence by Methyl Methanesulfonata Sensitive 2 Inhibition (2008)
  • Author(s): Min LJ, et. al.
  • Journal Title: Hypertension (in press)
  • Peer Reviewed
• [Journal Article] Reduction of angiotension II in the cerebrospinal fluid of patients with multiple sclerosis (2008)
  • Author(s): Kawajiri M, et. al.
  • Journal Title: Mult Scler (in press)
  • Peer Reviewed
• [Journal Article] Emerging concepts of regulation of angiotensin II receptors: new players and targets for traditional receptors (2008)
  • Author(s): Mogi M, et. al.
  • Journal Title: Arterioscler Thromb Vasc Biol 27 Pages: 2532-2539
  • Peer Reviewed
• [Journal Article] Emerging concepts of regulation of angiotensin II receptors : new players and targets for traditional receptors (2007)
  • Author(s): Mogi M., M. Iwai, and M. Horiuchi
  • Journal Title: Arterioscler Thromb Vasc Biol 27 Pages: 2532-2539
  • Peer Reviewed
• [Journal Article] Inhibition of cognitive decline in mice fed a high-salt and cholesterol diet by the angiotensin receptor blocker, olmesartan (2007)
  • Author(s): Mogi M., K. Tsukuda, J. M. Li et al
  • Journal Title: Neuropharmacology 53 Pages: 899-905
  • Peer Reviewed
• [Journal Article] Attenuation of monocyte chemoattractant protein-1 expression via inhibition of nuclear factor-kappaB activity in inflammatory vascular injury (2007)
  • Author(s): Gao X., M. Mogi, M. Horiuchi et al
  • Journal Title: Am J Hypertens 20 Pages: 1170-1175
  • Peer Reviewed
• [Journal Article] Pretreatment with eplerenone reduces stroke volume in mouse middle cerebral artery occlusion model (2007)
  • Author(s): Iwanami J., M. Mogi, M. Horiuchi et al
  • Journal Title: Eur J Pharmacol 566 Pages: 153-159
  • Peer Reviewed
• [Journal Article] Angiotensin II-induced neural differentiation via angiotensin II type 2 (AT2) receptor-MMS2 cascade involving interaction between AT2 receptor-interacting protein and Src homology 2 domain-containing protein-tyrosine phosphatase 1 (2007)
  • Author(s): Li J. M., M. Mogi, M. Horiuchi et al
  • Journal Title: Mol Endocrinol 21 Pages: 499-511
  • Peer Reviewed
• [Journal Article] Cross-talk between aldosterone and angiotensin II in vascular smooth muscle cell senescence (2007)
  • Author(s): Min L. J., M. Mogi, M. Horiuchi et al
  • Journal Title: Cardiovasc Res 76 Pages: 506-516
  • Peer Reviewed
• [Journal Article] Amelioration of cognitive impairment in the type-2 diabetic mouse by the angiotensin II type-1 receptor blocker candesartan (2007)
  • Author(s): Tsukuda K., M. Mogi, M. Horiuchi et al
  • Journal Title: Hypertension 50 Pages: 1099-1105
  • Peer Reviewed
• [Journal Article] 特集レニン・アンジオテンシン系 (2007)
  • Author(s): 茂木正樹、堀内正嗣
  • Journal Title: 脳梗塞とRAS内分泌・糖尿病科 25 Pages: 458-462
• [Journal Article] 特集脳から心血管障害を考える (2007)
  • Author(s): 茂木正樹、堀内正嗣
  • Journal Title: 血圧調節因子による脳梗塞修飾分子心血管病 8 Pages: 579-584
• [Journal Article] 特集降圧療法と脳血管障害 (2007)
  • Author(s): 茂木正樹、堀内正嗣
  • Journal Title: 高血圧によるラジカルストレスと脳血管系の傷害分子脳血管病 6 Pages: 384-389
• [Journal Article] 特集アンチエイジングに迫る (2007)
  • Author(s): 茂木正樹、堀内正嗣
  • Journal Title: レニン・アンジオテンシン系はアンチエイジングの鍵分子か? Life Science Medicine 1 Pages: 148-153
• [Journal Article] Amelioration of cognitive impairment in the type-2 diabetic mouse by the angiotensin type-1 receptor blocker candesartan (2007)
  • Author(s): Tsukuda K, et. al.
  • Journal Title: Hypertension 50 Pages: 1099-1105
  • Peer Reviewed
• [Journal Article] Inhibition of cognitive decline in mice fed a high-salt and cholesterol diet by the angiotensin receptor blocker, olmesartan (2007)
  • Author(s): Mogi M, et. al.
  • Journal Title: Neuropharmacology 53 Pages: 899-905
  • Peer Reviewed
• [Journal Article] 「特集 レニン・アンジオテンシ系」脳梗塞とRAS (2007)
  • Author(s): 茂木正樹, 也
  • Journal Title: 内分泌・糖尿病科 25 Pages: 458-462
• [Journal Article] 「特集 脳から心血管障害を考える」血圧調節因子による脳梗塞修飾 (2007)
  • Author(s): 茂木正樹, 也
  • Journal Title: 分子心血管病 8 Pages: 579-584
• [Journal Article] 「特集 降圧療法と脳血管障害」高血圧によるラジカルストレスと脳血管系の傷害 (2007)
  • Author(s): 茂木正樹, 也
  • Journal Title: 分子脳血管病 6 Pages: 384-389
• [Journal Article] 「特集 アンチイジングに迫る」7.レニン・アンジオテンシン系はアンチェイジングの鍵分子か? (2007)
  • Author(s): 茂木正樹, 也
  • Journal Title: Life Science Medicine 1 Pages: 148-153
• [Presentation] 血管平滑筋細胞におけるアルドステロンとAT1受容体の相互作用 (2008)
  • Author(s): 茂木正樹
  • Organizer: 第29回日本臨床薬理学会年会シンポジウム9
  • Place of Presentation: 東京
  • Year and Date: 2008-12-05
• [Presentation] 血管平滑筋細胞におけるアルドステロンとAT1受容体の相互作用 (2008)
  • Author(s): 茂木正樹
  • Organizer: 第29回日本臨床薬理学会年会シンポジウム9
  • Place of Presentation: 新宿
  • Year and Date: 2008-12-05
• [Presentation] アンチエイジングとレニン・アンジオテンシン系-脳の老化とアンジオテンシンー (2008)
  • Author(s): 茂木正樹
  • Organizer: 第12回日本心血管内分泌学会シンポジウム
  • Place of Presentation: 熊本
  • Year and Date: 2008-11-28
• [Presentation] アンチエイジングとレニン・アンジオテンシン系-脳の老化とアンジオテンシン- (2008)
  • Author(s): 茂木正樹
  • Organizer: 第12回日本心血管内分泌学会シンポジウム
  • Place of Presentation: 熊本
  • Year and Date: 2008-11-28
• [Presentation] Angiotensin II Type 1 Receptor-Associated Protein, ATRAP Suppresses Vascular Smooth Muscle Cell Senescence Partly due to an Inactivation of Calcineurin/nuclear Factor of Activated T Cells Pathway (2008)
  • Author(s): Mogi M
  • Organizer: 62nd Annual High Blood Pressure Research
  • Place of Presentation: Atlanta GA, USA
  • Year and Date: 2008-09-17
• [Presentation] Angiotensin II Type 1 Receptor Associated Protein, ATRAP Suppresses V ascular Smooth Muscle Cell Senescence Partly due to an Inactivation of Calcineurin/nuclear Factor of Activated T Cells Pathway. (2008)
  • Author(s): Mogi M
  • Organizer: 62^<nd> Annual High Blood Pressure Research
  • Place of Presentation: Atlanta, USA
  • Year and Date: 2008-09-17
• [Presentation] Renin angiotensin system in cerebrospinal fluid of patients with neurodegenerative diseases (2008)
  • Author(s): Mogi M
  • Organizer: 18th Scientific meeting International Society of Hypertension
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2008-07-17
• [Presentation] Effect of Renin Angiotensin System on Vascular Senescence ; Roles of AT1 Receptor, AT2 Receptor, Mineralocorticoid Receptor and ATRAP (2008)
  • Author(s): Mogi M
  • Organizer: 18th Scientific meeting International Society of Hypertension
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2008-07-17
• [Presentation] Effect of Renin Angiotensin System on Vascular Senescence; Roles of AT1 Recentor. AT2 Recentor. Mineralocorticoid Recentor and ATRAP (2008)
  • Author(s): Mogi M
  • Organizer: International Society of Hypertension 2008
  • Place of Presentation: Berlin, R
  • Year and Date: 2008-06-17
• [Presentation] Renin angiotensin system in cerebrospinal fluid of patients with neurode generative diseases. (2008)
  • Author(s): Mogi M
  • Organizer: International Society of Hypertension 2008
  • Place of Presentation: Berlin, BRP
  • Year and Date: 2008-06-07
• [Presentation] Angiotensin II Type 1 Receptor Blocker Telmisartan Prevented CognitiveDecline in Amyloid Beta-Injected Mice (2008)
  • Author(s): Mogi M
  • Organizer: European Stroke Conference 2008
  • Place of Presentation: Nice, France
  • Year and Date: 2008-05-14
• [Presentation] Angiotensin II Type 1 Receptor Blocker Telmisartan Prevented Cognitive Decline in Amyloid Beta-Injected Mice (2008)
  • Author(s): Mogi M
  • Organizer: European Stroke Conference 2008
  • Place of Presentation: Nice, France
  • Year and Date: 2008-05-14
• [Presentation] 基礎実験から見た脳卒中・認知機能低下への降圧療法の選択脳内レニン・アンジオテンシン系の役割 (2008)
  • Author(s): 茂木正樹
  • Organizer: 第33回日本脳卒中学会総会シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2008-03-20
• [Presentation] Effect of renin angiotensin system in vascular senescence ; roles of AT1 receptor, AT2 receptor, mineralocorticoid receptor and ATRAP (2008)
  • Author(s): Mogi M
  • Organizer: Gordon Research Conference 2008 Angiotensin
  • Place of Presentation: Ventura CA, USA
  • Year and Date: 2008-02-26
• [Presentation] Effect of renin angiotensin system on vascular senescence; roles of AT_1 receptor, AT_2 receptor, mineralocorticoid receptor and ATPRAP (2008)
  • Author(s): Mogi M
  • Organizer: Cordon Research Conference 2008
  • Place of Presentation: Ventura, CA, USA: Four Points Sheraton in Ventura
  • Year and Date: 2008-02-25
• [Presentation] 脳神経疾患とアンジオテンシン (2007)
  • Author(s): 茂木正樹
  • Organizer: 第30回日本高血圧学会学術総会シンポジウム1
  • Place of Presentation: 沖縄
  • Year and Date: 2007-10-25
• [Presentation] 脳神経疾患とアンジオテンシン (2007)
  • Author(s): 茂木正樹
  • Organizer: 第30回日本高血圧学会学術総会シンポジウム1:レニン・アンジオテンシン・アルドステロン系の新しい展開
  • Place of Presentation: 沖縄:沖縄コンベンションセンター
  • Year and Date: 2007-10-25
• [Presentation] New protective role of AT2 receptor stimulation in vascular smooth muscle cell senescence involving methyl methanesulfonate sensitive 2 (2007)
  • Author(s): Mogi M
  • Organizer: 61st Annual High Blood Pressure Research
  • Place of Presentation: Tucson AZ, USA
  • Year and Date: 2007-09-26
• [Presentation] New protective role of AT_2 receptor stimulation in vascular smooth muscle cell senescence involving methyl methansulfonate sensitive 2 (2007)
  • Author(s): Mogi M
  • Organizer: 61st High Blood Pressure Research Conference 2007
  • Place of Presentation: Tucson, AZ, USA: Westin La Paloma
  • Year and Date: 2007-09-25
• [Presentation] 血管平滑筋細胞の老化におけるアンジオテンシンII2型受容体の役割についての検討-MMS2によるDNA修復機構の関与- (2007)
  • Author(s): 茂木正樹
  • Organizer: 第49回日本老年医学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2007-06-22
• [Presentation] 血管平滑筋細胞の老化におけるアンジオテンシンII 2型受容体の役割についての検討-MMS2によるDNA修復機構の関与ー (2007)
  • Author(s): 茂木正樹
  • Organizer: 第49回日本老年医学会学術集会
  • Place of Presentation: 札幌:ロイトン札幌
  • Year and Date: 2007-06-22
• [Presentation] ACE阻害薬とARBの心血管イベント抑制効果 (2007)
  • Author(s): 茂木正樹
  • Organizer: 第80回日本内分泌学会学術総会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2007-06-16
• [Presentation] ACE阻害薬とARBの心血管イベント抑制効果 C-13-2 ARBによる脳保護作用 (2007)
  • Author(s): 茂木正樹
  • Organizer: 第80回日本内分泌学会学術総会 シンポジウム;クリニカルアワー
  • Place of Presentation: 東京:東京国際フォーラム
  • Year and Date: 2007-06-16
• [Book] 酸化ストレスと心血管病「酸化ストレスとアンジオテンシン」 (2007)
  • Author(s): 茂木正樹他
  • Publisher: 日本医学出版
• [Book] 単行本『高血圧ナビゲーター』第4章発症機序・病態4.AT1受容体 (2007)
  • Author(s): 茂木正樹他
  • Publisher: メディカルレビュー社
• [Book] 単行本『高血圧ナビゲーター』第4章 発症機序・病態 4.AT_1受容体 (2007)
  • Author(s): 茂木正樹, 他
  • Publisher: メディカルレビュー社