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Lipocalin 2 modulates the cellular response to amyloid beta.

ABSTRACT: The production, accumulation and aggregation of amyloid beta (A?) 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 A? aggregation. Herein, we describe that lipocalin 2 (LCN2), a mammalian acute-phase protein involved in iron homeostasis, is highly produced in response to A?1-42 by choroid plexus epithelial cells and astrocytes, but not by microglia or neurons. Although A?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 A? toxicity to astrocytes requires LCN2, which represents a novel mechanism to target when addressing AD.

SUBMITTER: Mesquita SD

PROVIDER: S-EPMC4158684 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Lipocalin 2 modulates the cellular response to amyloid beta.

Mesquita S D SD Ferreira A C AC Falcao A M AM Sousa J C JC Oliveira T G TG Correia-Neves M M Sousa N N Marques F F Palha J A JA

Cell death and differentiation 20140523 10

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, b ...[more]

PMID: 24853299

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