阿部 陽一郎 (アベ ヨウイチロウ)

Abe, Yoichiro

写真a

所属(所属キャンパス)

医学部 薬理学教室 (信濃町)

職名

助教

外部リンク

経歴 【 表示 / 非表示

  • 1997年04月
    -
    1999年03月

    筑波大学基礎医学系, 薬理学, リサーチアソシエート

  • 1999年04月
    -
    2007年03月

    慶應義塾大学医学部, 薬理学, 助手

  • 2007年04月
    -
    2009年03月

    慶應義塾大学医学部, 薬理学, 助教

  • 2009年04月
    -
    継続中

    慶應義塾大学医学部, 薬理学, 講師

学位 【 表示 / 非表示

  • 博士(医学), 筑波大学, 課程

 

研究分野 【 表示 / 非表示

  • ライフサイエンス / 分子生物学

  • ライフサイエンス / 薬理学

研究キーワード 【 表示 / 非表示

  • アクアポリン4

  • アストロサイト

  • 神経変性疾患

  • 視神経脊髄炎

 

論文 【 表示 / 非表示

  • Aquaporin-4 in Neuromyelitis Optica Spectrum Disorders: A Target of Autoimmunity in the Central Nervous System

    Abe Y., Yasui M.

    Biomolecules (Biomolecules)  12 ( 4 )  2022年04月

     概要を見る

    Since the discovery of a specific autoantibody in patients with neuromyelitis optica spectrum disorder (NMOSD) in 2004, the water channel aquaporin-4 (AQP4) has attracted attention as a target of autoimmune diseases of the central nervous system. In NMOSD, the autoantibody (NMO-IgG) binds to the extracellular loops of AQP4 as expressed in perivascular astrocytic end-feet and disrupts astrocytes in a complement-dependent manner. NMO-IgG is an excellent marker for distinguishing the disease from other inflammatory demyelinating diseases, such as multiple sclerosis. The unique higher-order structure of AQP4—called orthogonal arrays of particles (OAPs)—as well as its subcellular localization may play a crucial role in the pathogenesis of the disease. Recent studies have also demonstrated complement-independent cytotoxic effects of NMO-IgG. Antibody-induced endocytosis of AQP4 has been suggested to be involved in this mechanism. This review focuses on the binding properties of antibodies that recognize the extracellular region of AQP4 and the characteristics of AQP4 that are implicated in the pathogenesis of NMOSD.

  • Quantitative measurement of diffusion-weighted imaging signal using expression-controlled aquaporin-4 cells: Comparative study of 2-compartment and diffusion kurtosis imaging models

    Imaizumi A., Obata T., Kershaw J., Tachibana Y., Abe Y., Shibata S., Nitta N., Aoki I., Yasui M., Higashi T.

    PLoS ONE (PLoS ONE)  17 ( 4 April )  2022年04月

     概要を見る

    The purpose of this study was to compare parameter estimates for the 2-compartment and diffusion kurtosis imaging models obtained from diffusion-weighted imaging (DWI) of aquaporin-4 (AQP4) expression-controlled cells, and to look for biomarkers that indicate differences in the cell membrane water permeability. DWI was performed on AQP4-expressing and non-expressing cells and the signal was analyzed with the 2-compartment and diffusion kurtosis imaging models. For the 2-compartment model, the diffusion coefficients (Df, Ds) and volume fractions (Ff, Fs, Ff = 1-Fs) of the fast and slow compartments were estimated. For the diffusion kurtosis imaging model, estimates of the diffusion kurtosis (K) and corrected diffusion coefficient (D) were obtained. For the 2-compartment model, Ds and Fs showed clear differences between AQP4-expressing and non-expressing cells. Fs was also sensitive to cell density. There was no clear relationship with the cell type for the diffusion kurtosis imaging model parameters. Changes to cell membrane water permeability due to AQP4 expression affected DWI of cell suspensions. For the 2-compartment and diffusion kurtosis imaging models, Ds was the parameter most sensitive to differences in AQP4 expression.

  • Glymphatic system clears extracellular tau and protects from tau aggregation and neurodegeneration

    Ishida K., Yamada K., Nishiyama R., Hashimoto T., Nishida I., Abe Y., Yasui M., Iwatsubo T.

    Journal of Experimental Medicine (Journal of Experimental Medicine)  219 ( 3 )  2022年03月

    ISSN  00221007

     概要を見る

    Accumulation of tau has been implicated in various neurodegenerative diseases termed tauopathies. Tau is a microtubule-associated protein but is also actively released into the extracellular fluids including brain interstitial fluid and cerebrospinal fluid (CSF). However, it remains elusive whether clearance of extracellular tau impacts tau-associated neurodegeneration. Here, we show that aquaporin-4 (AQP4), a major driver of the glymphatic clearance system, facilitates the elimination of extracellular tau from the brain to CSF and subsequently to deep cervical lymph nodes. Strikingly, deletion of AQP4 not only elevated tau in CSF but also markedly exacerbated phosphorylated tau deposition and the associated neurodegeneration in the brains of transgenic mice expressing P301S mutant tau. The current study identified the clearance pathway of extracellular tau in the central nervous system, suggesting that glymphatic clearance of extracellular tau is a novel regulatory mechanism whose impairment contributes to tau aggregation and neurodegeneration.

  • The α-dystrobrevins play a key role in maintaining the structure and function of the extracellular matrix–significance for protein elimination failure arteriopathies

    Sharp M.M.G., Cassidy J., Thornton T., Lyles J., Keable A., Gatherer M., Yasui M., Abe Y., Shibata S., Weller R.O., Górecki D.C., Carare R.O.

    Acta Neuropathologica Communications (Acta Neuropathologica Communications)  9 ( 1 )  2021年12月

     概要を見る

    The extracellular matrix (ECM) of the cerebral vasculature provides a pathway for the flow of interstitial fluid (ISF) and solutes out of the brain by intramural periarterial drainage (IPAD). Failure of IPAD leads to protein elimination failure arteriopathies such as cerebral amyloid angiopathy (CAA). The ECM consists of a complex network of glycoproteins and proteoglycans that form distinct basement membranes (BM) around different vascular cell types. Astrocyte endfeet that are localised against the walls of blood vessels are tethered to these BMs by dystrophin associated protein complex (DPC). Alpha-dystrobrevin (α-DB) is a key dystrophin associated protein within perivascular astrocyte endfeet; its deficiency leads to a reduction in other dystrophin associated proteins, loss of AQP4 and altered ECM. In human dementia cohorts there is a positive correlation between dystrobrevin gene expression and CAA. In the present study, we test the hypotheses that (a) the positive correlation between dystrobrevin gene expression and CAA is associated with elevated expression of α-DB at glial-vascular endfeet and (b) a deficiency in α-DB results in changes to the ECM and failure of IPAD. We used human post-mortem brain tissue with different severities of CAA and transgenic α-DB deficient mice. In human post-mortem tissue we observed a significant increase in vascular α-DB with CAA (CAA vrs. Old p < 0.005, CAA vrs. Young p < 0.005). In the mouse model of α-DB deficiency, there was early modifications to vascular ECM (collagen IV and BM thickening) that translated into reduced IPAD efficiency. Our findings highlight the important role of α-DB in maintaining structure and function of ECM, particularly as a pathway for the flow of ISF and solutes out of the brain by IPAD.

  • Di-lysine motif-like sequences formed by deleting the C-terminal domain of aquaporin-4 prevent its trafficking to the plasma membrane

    Chau S., Fujii A., Wang Y., Vandebroek A., Goda W., Yasui M., Abe Y.

    Genes to Cells (Genes to Cells)  26 ( 3 ) 152 - 164 2021年03月

    ISSN  13569597

     概要を見る

    Aquaporin-4 is a transmembrane water channel protein, the C-terminal domain of which is facing the cytosol. In the process of investigating the role of the C-terminal domain of aquaporin-4 with regard to intracellular trafficking, we observed that a derivative of aquaporin-4, in which the C-terminal 53 amino acids had been removed (Δ271-323), was localized to intracellular compartments, including the endoplasmic reticulum, but was not expressed on the plasma membranes. This was determined by immunofluorescence staining and labeling of the cells with monoclonal antibody specifically recognizing the extracellular domain of aquaporin-4, followed by confocal microscopy and flow cytometry. Deletion of additional amino acids in the C-terminal domain of aquaporin-4 led to its redistribution to the plasma membrane. This suggests that the effect of the 53-amino acid deletion on the subcellular localization of aquaporin-4 could be attributed to the formation of a signal at the C terminus that retained aquaporin-4 in intracellular compartments, rather than the loss of a signal required for plasma membrane targeting. Substitution of the lysine at position 268 with alanine could rescue the Δ271-323-associated retention in the cytosol, suggesting that the C-terminal sequence of the mutant served as a signal similar to a di-lysine motif.

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

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研究発表 【 表示 / 非表示

  • Development of a new Neuromyelitis Optica model mice.

    Chau SH, Abe Y, Yasui M

    The 18th World Congress of Basic and Clinical Pharmacology/The 91st Annual Meeting of the Japanese Pharmacological Society (京都) , 

    2018年07月

    ポスター発表, 日本薬理学会

  • Roles of the C-terminal domain in intracellular trafficking and degradation of AQP4.

    阿部 陽一郎

    The 40th Annual Meeting of the Molecular Biology Society of Japan (Kobe) , 

    2017年12月

    ポスター発表

  • Aquaporin-4 is not involved in chronic neuroinflammatory responses in 5xFAD mice.

    阿部 陽一郎,

    The 90th Annual Meeting of the Japanese Pharmacological Society (長崎) , 

    2017年03月

    ポスター発表

  • Glial responses to amyloid β accumulation in aquaporin-4-deficient Alzheimer’s disease model.

    Abe, Y., Chau, S., Wada, H., Yasui, M., and Niikura, T.

    The 39th Annual Meeting of the Japan Neuroscience Society (Yokohama) , 

    2016年07月

    ポスター発表

  • High avidity chimeric monoclonal antibodies against the extracellular domains of human aquaporin-4 competing with NMO-IgG.

    Miyazaki-Komine, K, Abe, Y., Huang, P., Takai, Y., Kusano-Arai, O., Iwanari, H., Misu, T., Sakihama, T., Toyama, Y., Fujihara, K., Hamakubo, T., and Yasui, M.

    The 88th Annual Meeting of the Japanese Pharmacological Society (Nagoya) , 

    2015年03月

    ポスター発表

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競争的研究費の研究課題 【 表示 / 非表示

  • アクアポリン4機能と脳リンパ排泄機構に着目したアルツハイマー病発症機構の解明

    2017年04月
    -
    2019年03月

    日本学術振興会, 科学研究費補助金(文部科学省・日本学術振興会), 阿部陽一郎, 補助金,  研究代表者

  • 視神経脊髄炎の動物モデルと抗アクアポリン4抗体を用いた新規治療法の開発基盤研究

    2016年04月
    -
    2019年03月

    日本学術振興会, 科学研究費補助金(文部科学省・日本学術振興会), 阿部陽一郎, 補助金,  研究代表者

  • アルツハイマー病モデルマウスを用いたAβ蓄積から神経原繊維変化へ至る機構の解明

    2013年04月
    -
    2015年03月

    日本学術振興会, 科学研究費補助金(文部科学省・日本学術振興会), 阿部陽一郎, 補助金,  研究代表者

  • アクアポリン4ノックアウトマウスを用いた新規視神経脊髄炎モデルの作製とその解析

    2010年04月
    -
    2013年03月

    日本学術振興会, 科学研究費補助金(文部科学省・日本学術振興会), 阿部陽一郎, 補助金,  研究代表者

  • FALS変異SOD1導入ES細胞由来in vitroモデル神経細胞の樹立と解析

    2004年04月
    -
    2006年03月

    日本学術振興会, 科学研究費補助金(文部科学省・日本学術振興会), 阿部陽一郎, 補助金,  研究代表者

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担当授業科目 【 表示 / 非表示

  • 薬理学

    2022年度

  • 薬理学

    2021年度

  • 薬理学

    2020年度

  • 薬理学

    2019年度

担当経験のある授業科目 【 表示 / 非表示

  • 薬理学

    慶應義塾

    2015年04月
    -
    2016年03月

    春学期

 

所属学協会 【 表示 / 非表示

  • 日本分子生物学会, 

    2011年
    -
    継続中
  • 日本神経科学学会, 

    2008年
    -
    継続中
  • Society for Neuroscience, 

    2003年
    -
    継続中
  • 日本再生医療学会, 

    2002年
    -
    2010年
  • 日本薬理学会, 

    1993年
    -
    継続中