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Matrix metalloproteinase (MMP) system in brain: identification and characterization of brain-specific MMP highly expressed in cerebellum

Authors

  • Yoko Sekine-Aizawa,

    1. Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2–1 Hirosawa, Wako-shi, Saitama, 351–0198 Japan
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    • *Present address: Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore MD, 21205 USA
  • Emi Hama,

    1. Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2–1 Hirosawa, Wako-shi, Saitama, 351–0198 Japan
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  • Kaori Watanabe,

    1. Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2–1 Hirosawa, Wako-shi, Saitama, 351–0198 Japan
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  • Satoshi Tsubuki,

    1. Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2–1 Hirosawa, Wako-shi, Saitama, 351–0198 Japan
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  • Masami Kanai-Azuma,

    1. Department of Ultrastructural Research, The Tokyo Metropolitan Institute of Medical Science, 3–18–22 Honkomagome, Bunkyo-ku, Tokyo,113–8613 Japan
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  • Yoshiakira Kanai,

    1. Department of Veterinary Anatomy, University of Tokyo, 1–1 Yayoi, Bunkyo-ku, Tokyo, 113–8657 Japan
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  • Hiroyuki Arai,

    1. Department of Geriatric Medicine, Tohoku University School of Medicine, 1–1 Seiryo-Machi, Aoba-ku, Sendai, 980–77 Japan
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  • Hiroyuki Aizawa,

    1. Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2–1 Hirosawa, Wako-shi, Saitama, 351–0198 Japan
    2. Department of Cell Biology, The Tokyo Metropolitan Institute of Medical Science, 3–18–22 Honkomagome, Bunkyo-ku, Tokyo,113–8613 Japan
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    • *Present address: Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore MD, 21205 USA
  • Nobuhisa Iwata,

    1. Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2–1 Hirosawa, Wako-shi, Saitama, 351–0198 Japan
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  • Takaomi C. Saido

    1. Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, 2–1 Hirosawa, Wako-shi, Saitama, 351–0198 Japan
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: Dr Takaomi C.Saido, as above.
E-mail: saido@brain.riken.go.jp

Abstract

The matrix metalloproteinase (MMP) family, comprising more than 20 isoforms, modulates the extracellular milieu by degrading extracellular matrix (ECM) proteins. Because MMP is one of the few groups of proteinases capable of hydrolysing insoluble fibrillar proteins, they are likely to play crucial roles in regulating both normal and pathophysiological processes in the brain. However, little is yet known about their possible neuronal functions due presumably to their unusual redundancy and to the absence of a complete catalogue of isoforms. As an initial step in understanding the MMP system in the brain, we analysed an expression spectrum of MMP in rat brain using RT-PCR and discovered a novel brain-specific MMP, MT5-MMP. MT5-MMP was the predominant species among the nongelatinase-type isoforms in brain. MT5-MMP, present in all brain tissues examined, was most strongly expressed in cerebellum and was localized in the membranous structures of expressing neurons, as assessed biochemically and immunohistochemically. In cerebellum, its expression was regulated developmentally and was closely associated with dendritic tree formation of Purkinje cells, suggesting that MT5-MMP may contribute to neuronal development. Furthermore, its stable postdevelopmental expression and colocalization with senile plaques in Alzheimer brain indicates possible roles in neuronal remodeling naturally occurring in adulthood and in regulating pathophysiological processes associated with advanced age.

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