Abstract
The production, accumulation and aggregation of amyloid beta (Aβ) peptides in Alzheimer's disease (AD) are influenced by different modulators. Among these are iron and iron-related proteins, given their ability to modulate the expression of the amyloid precursor protein and to drive Aβ aggregation. Herein, we describe that lipocalin 2 (LCN2), a mammalian acute-phase protein involved in iron homeostasis, is highly produced in response to Aβ 1-42 by choroid plexus epithelial cells and astrocytes, but not by microglia or neurons. Although Aβ 1-42 stimulation decreases the dehydrogenase activity and survival of wild-type astrocytes, astrocytes lacking the expression of Lcn2 are not affected. This protection results from a lower expression of the proapoptotic gene Bim and a decreased inflammatory response. Altogether, these findings show that Aβ toxicity to astrocytes requires LCN2, which represents a novel mechanism to target when addressing AD.
Original language | English (US) |
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Pages (from-to) | 1588-1599 |
Number of pages | 12 |
Journal | Cell Death and Differentiation |
Volume | 21 |
Issue number | 10 |
DOIs | |
State | Published - Oct 1 2014 |
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology