β-Secretase activity in rat astrocytes: translational block of BACE1 and modulation of BACE2 expression

Authors

  • Barbara Bettegazzi,

    1. San Raffaele Scientific Institute, via Olgettina 58, I-20132, Milano, Italy
    2. Vita-Salute San Raffaele University, Milano, Italy
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    • B.B. and M.M. contributed equally to this work.

  • Marija Mihailovich,

    1. San Raffaele Scientific Institute, via Olgettina 58, I-20132, Milano, Italy
    2. Vita-Salute San Raffaele University, Milano, Italy
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    • B.B. and M.M. contributed equally to this work.

  • Alessandra Di Cesare,

    1. San Raffaele Scientific Institute, via Olgettina 58, I-20132, Milano, Italy
    2. Vita-Salute San Raffaele University, Milano, Italy
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  • Alessandra Consonni,

    1. San Raffaele Scientific Institute, via Olgettina 58, I-20132, Milano, Italy
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  • Romina Macco,

    1. San Raffaele Scientific Institute, via Olgettina 58, I-20132, Milano, Italy
    2. Vita-Salute San Raffaele University, Milano, Italy
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  • Ilaria Pelizzoni,

    1. San Raffaele Scientific Institute, via Olgettina 58, I-20132, Milano, Italy
    2. Vita-Salute San Raffaele University, Milano, Italy
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  • Franca Codazzi,

    1. San Raffaele Scientific Institute, via Olgettina 58, I-20132, Milano, Italy
    2. Italian Institute of Technology, Research Unit of Molecular Neuroscience, Milano, Italy
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  • Fabio Grohovaz,

    1. San Raffaele Scientific Institute, via Olgettina 58, I-20132, Milano, Italy
    2. Vita-Salute San Raffaele University, Milano, Italy
    3. Italian Institute of Technology, Research Unit of Molecular Neuroscience, Milano, Italy
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  • Daniele Zacchetti

    1. San Raffaele Scientific Institute, via Olgettina 58, I-20132, Milano, Italy
    2. Italian Institute of Technology, Research Unit of Molecular Neuroscience, Milano, Italy
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Daniele Zacchetti and Fabio Grohovaz, Dibit, 1San Raffaele Scientific Institute, as above.
E-mails: zacchetti.daniele@hsr.it and grohovaz.fabio@hsr.it

Abstract

BACE1 and BACE2 are two closely related membrane-bound aspartic proteases. BACE1 is widely recognized as the neuronal β-secretase that cleaves the amyloid-β precursor protein, thus allowing the production of amyloid-β, i.e. the peptide that has been proposed to trigger the neurodegenerative process in Alzheimer’s disease. BACE2 has ubiquitous expression and its physiological and pathological role is still unclear. In light of a possible role of glial cells in the accumulation of amyloid-β in brain, we have investigated the expression of these two enzymes in primary cultures of astrocytes. We show that astrocytes possess β-secretase activity and produce amyloid-β because of the activity of BACE2, but not BACE1, the expression of which is blocked at the translational level. Finally, our data demonstrate that changes in the astrocytic phenotype during neuroinflammation can produce both a negative as well as a positive modulation of β-secretase activity, also depending on the differential responsivity of the brain regions.

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