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

被引：26

作者：

Bettegazzi, Barbara ^{[1
,2
]}

Mihailovich, Marija ^{[1
,2
]}

Di Cesare, Alessandra ^{[1
,2
]}

Consonni, Alessandra ^{[1
]}

Macco, Romina ^{[1
,2
]}

Pelizzoni, Ilaria ^{[1
,2
]}

Codazzi, Franca ^{[1
,3
]}

Grohovaz, Fabio ^{[1
,2
,3
]}

Zacchetti, Daniele ^{[1
,3
]}

机构：

[1] Ist Sci San Raffaele, I-20132 Milan, Italy

[2] Univ Vita Salute San Raffaele, Milan, Italy

[3] Italian Inst Technol, Res Unit Mol Neurosci, Milan, Italy

来源：

EUROPEAN JOURNAL OF NEUROSCIENCE | 2011年 / 33卷 / 02期

关键词：

Alzheimer's disease; amyloid-beta; astrocyte activation; protein translation; AMYLOID PRECURSOR PROTEIN; ALZHEIMERS-DISEASE; CLEAVING ENZYME-1; INTERFERON-GAMMA; IN-VITRO; MICE; SITE; PEPTIDE; CELLS; BRAIN;

D O I：

10.1111/j.1460-9568.2010.07482.x

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

BACE1 and BACE2 are two closely related membrane-bound aspartic proteases. BACE1 is widely recognized as the neuronal beta-secretase that cleaves the amyloid-beta precursor protein, thus allowing the production of amyloid-beta, 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-beta in brain, we have investigated the expression of these two enzymes in primary cultures of astrocytes. We show that astrocytes possess beta-secretase activity and produce amyloid-beta 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 beta-secretase activity, also depending on the differential responsivity of the brain regions.

引用

页码：236 / 243

页数：8

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