JP5907563B2 - アミロイドβ神経障害バイオマーカー - Google Patents
アミロイドβ神経障害バイオマーカー Download PDFInfo
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- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
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Description
factor 8)は,lactadherin;P47;Mfgm;SED1などとも呼称される分泌タンパク質であり(GenBank No. NP_032620.2,IPI No. IPI00788387.1)
,2つの機能的ドメインを持つ(N末端にEGFドメイン,C末端にC2ドメイン)。これはL型(72kDa,61kDa)とS型(56kDa,48kDa)のアイソフォームを持ち,L型が分泌タイプであると報告されている(図1)。
Pharmacol (2008) 3:246-256)は,ミクログリア由来細胞株を用いてMFG-E8の動態を調べ,脳内においてはミクログリア細胞がMFG-E8を産生し,MFG-E8がアポトーシスを起こした神経芽腫細胞を認識して,貪食において役割を果たす可能性を報告している。これは,末梢血においてマクロファージがMFG-E8を産生し,MFG-E8がアポトーシスを起こした細胞を認識してこれをマクロファージに伝える機能と対応するものと考えられる。一方,Fullerらはさらに実験を重ねた結果,ヒト家族性アルツハイマー病のAPP遺伝子を有するTGマウス(アルツハイマーモデルマウス)では,正常マウスと比較して脳内のMFG-E8のレベルが低下していることを見いだした。このことに関しては,MFG-E8の制御の乱れがアルツハイマー病の進行に何らかの役割を果たしているのではないかと解釈している。同様に,Boddaert Jら(Am J Pathol (2007) 170:921-929)も,アルツハイマー病の脳において同年齢の脳に比べMFG-E8のmRNA発現が低下している事実を示している。
認知症のモデルとして,Aβ42ペプチドで細胞障害を与えたマウス初代神経培養細胞を用い,脳生体膜を模倣した磁性ナノリポソームを用いて,アミロイドβ神経障害バイオマーカー候補を探索した。Aβ42はアミロイドプリカーサプロテイン:APP(150KD)から3種類の酵素で切断されてできる最終産物のなかの一つであり,最も細胞毒性が強く,多くの研究で使用されているものである。
isoform 1)が同定された。
次に,ウエスタンブロットにてタンパク質レベルでのMFG-E8の発現量の差を確認した。
アルツハイマー病(AD)患者および年齢の対応した健常老人の血漿中のMFG-E8濃度を,ELISAにより測定した。
Claims (5)
- アルツハイマー病を検査するための方法であって,被験者または被検動物から得た血液,血清または血漿試料中のMFG-E8蛋白質の量を測定し,得られた測定値をアルツハイマー病の診断の指標とすることを特徴とする方法。
- MFG-E8蛋白質の量が抗MFG-E8抗体を用いて測定される,請求項1に記載の方法。
- 抗MFG-E8抗体を含むアルツハイマー病の血液,血清または血漿検査薬。
- 抗MFG-E8抗体と,抗MFG-E8抗体と結合したMFG-E8蛋白質を検出するための試薬とを含むアルツハイマー病の血液,血清または血漿検査キット。
- アルツハイマー病の治療薬の候補物質を選択する方法であって,
試験物質を作用させたモデル細胞の培養液中または試験物質を作用させたモデル動物から得た血液,血清または血漿試料中のMFG-E8蛋白質の量を測定し,そして,
試験物質を作用させたときに作用させていないときと比較してMFG-E8蛋白質の量が低い場合に,その試験物質をアルツハイマー病の治療薬の候補物質として選択する,
の各工程を含む方法。
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Application Number | Priority Date | Filing Date | Title |
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JP2010280331 | 2010-12-16 | ||
JP2010280331 | 2010-12-16 | ||
PCT/JP2011/078036 WO2012081433A1 (ja) | 2010-12-16 | 2011-12-05 | アミロイドβ神経障害バイオマーカー |
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JPWO2012081433A1 JPWO2012081433A1 (ja) | 2014-05-22 |
JP5907563B2 true JP5907563B2 (ja) | 2016-04-26 |
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US (1) | US20130302838A1 (ja) |
EP (1) | EP2653872B1 (ja) |
JP (1) | JP5907563B2 (ja) |
ES (1) | ES2625529T3 (ja) |
WO (1) | WO2012081433A1 (ja) |
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US20200309788A1 (en) * | 2017-09-29 | 2020-10-01 | The General Hospital Corporation | Methods for identifying and treating adrenomyeloneuropathy (amn) |
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EP2653872B1 (en) | 2017-02-22 |
EP2653872A4 (en) | 2014-12-24 |
ES2625529T3 (es) | 2017-07-19 |
JPWO2012081433A1 (ja) | 2014-05-22 |
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WO2012081433A1 (ja) | 2012-06-21 |
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