• Open Access

Neuroprotective role of γ-enolase in microglia in a mouse model of Alzheimer's disease is regulated by cathepsin X

Authors

  • Anja Hafner,

    1. Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
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  • Gordana Glavan,

    1. Institute of Pathophysiology, Medical faculty, University of Ljubljana, Ljubljana, Slovenia
    2. Department of Biology, Biotechnical faculty, University of Ljubljana, Ljubljana, Slovenia
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  • Nataša Obermajer,

    1. Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
    2. Department of Biotechnology, Jožef Stefan Institute, Ljubljana, Slovenia
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  • Marko Živin,

    1. Institute of Pathophysiology, Medical faculty, University of Ljubljana, Ljubljana, Slovenia
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  • Reinhard Schliebs,

    1. Department of Neurochemistry, Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany
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  • Janko Kos

    Corresponding author
    1. Department of Biotechnology, Jožef Stefan Institute, Ljubljana, Slovenia
    • Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
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Correspondence

Professor Janko Kos, Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia. Tel.: +386 47 69 604; fax: +386 42 58 031; e-mail: janko.kos@ffa.uni-lj.si

Summary

γ-Enolase is a neurotrophic-like factor promoting growth, differentiation, survival and regeneration of neurons. Its neurotrophic activity is regulated by cysteine protease cathepsin X which cleaves the C-terminal end of the molecule. We have investigated the expression and colocalization of γ-enolase and cathepsin X in brains of Tg2576 mice overexpressing amyloid precursor protein. In situ hybridization of γ-enolase and cathepsin X revealed that mRNAs for both enzymes were expressed abundantly around amyloid plaques. Immunostaining demonstrated that the C-terminally cleaved form of γ-enolase was present in the immediate plaque vicinity, whereas the intact form, exhibiting neurotrophic activity, was observed in microglia cells in close proximity to senile plaque. The upregulation of γ-enolase in microglial cells in response to amyloid-β peptide (Aβ) was confirmed in mouse microglial cell line EOC 13.31 and primary microglia and medium enriched with γ-enolase proved to be neuroprotective against Aβ toxicity; however, the effect was reversed by cathepsin X proteolytic activity. These results demonstrate an upregulation of γ-enolase in microglia cells surrounding amyloid plaques in Tg2576 transgenic mice and demonstrate its neuroprotective role in amyloid-β-related neurodegeneration.

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