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

Barbara Bettegazzi, Marija Mihailovich, Alessandra Di Cesare, Alessandra Consonni, Romina Macco, Ilaria Pelizzoni, Franca Codazzi, Fabio Grohovaz, Daniele Zacchetti

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)236-243
Number of pages8
JournalEuropean Journal of Neuroscience
Volume33
Issue number2
DOIs
Publication statusPublished - Jan 2011

Keywords

  • Alzheimer's disease
  • Amyloid-β
  • Astrocyte activation
  • Protein translation

ASJC Scopus subject areas

  • Neuroscience(all)

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