title: β-Secretase activity in rat astrocytes: translational block of BACE1 and modulation of BACE2 expression.
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.
authors.affiliation: San Raffaele Scientific Institute, via Olgettina 58, I-20132, Milano, Italy Vita-Salute San Raffaele University, Milano, Italy Italian Institute of Technology, Research Unit of Molecular Neuroscience, Milano, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bettegazzi
authors.forename: Marija
authors.initials: M
authors.lastname: Mihailovich
authors.forename: Alessandra
authors.initials: A
authors.lastname: Di Cesare
authors.forename: Alessandra
authors.initials: A
authors.lastname: Consonni
authors.forename: Romina
authors.initials: R
authors.lastname: Macco
authors.forename: Ilaria
authors.initials: I
authors.lastname: Pelizzoni
authors.forename: Franca
authors.initials: F
authors.lastname: Codazzi
authors.forename: Fabio
authors.initials: F
authors.lastname: Grohovaz
authors.forename: Daniele
authors.initials: D
authors.lastname: Zacchetti
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000166:cytology / Q000201:enzymology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D014176:Protein Biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509287:Bace2 protein, rat; C509281:Bace1 protein, rat