新規軸索再生阻害因子RGMの同定とその機能の解明

発生期には、軸索を誘導する因子が適切な神経回路の形成に必須の役割を担う。このうち軸索を反発させる因子は成長円錐を虚脱させ、軸索を腿縮させることから、成体の中枢神経では再生阻害に働いているのではないかと考えられる。実際に脊髄損傷周辺部に複数の軸索反発因子の発現が高まってくることがわかっている。GPIアンカー型タンパク質であるRepulsive guidance molecule (RGM)は、胎生期において網膜や海馬の神経細胞の軸索誘導や神経管の閉鎖に関与するタンパク質であるが、脊髄損傷の後にも損傷部で発現の増加がみられる。ラットの脊髄損傷後に、RGMの効果を中和する抗体を損傷局所に投与したところ、有意な運動機能改善と皮質脊髄路の再生が認められた(図５；Hata et al., J. Cell Biol.,2006)。私たちはRGMがどのように神経細胞に働きかけるのか、その分子機構の解明を行った(図６；Hata et al., J. Cell Biol.,2009; Endo et al., J. Neurosci., 2009)。さらにRGMの惹起する幅広いシグナルが様々な生命現象に関わることを見いだした（参考論文参照）。

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参考論文

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