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Cell Death Differ. 2014 Oct;21(10):1588-99. doi: 10.1038/cdd.2014.68. Epub 2014 May 23.

Lipocalin 2 modulates the cellular response to amyloid beta.

Author information

1
1] Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal [2] ICVS/3B's-PT Government Associate Laboratory, Guimaraes, Portugal.

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 Aβ1-42 by choroid plexus epithelial cells and astrocytes, but not by microglia or neurons. Although Aβ1-42 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.

PMID:
24853299
PMCID:
PMC4158684
DOI:
10.1038/cdd.2014.68
[Indexed for MEDLINE]
Free PMC Article

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