Lipocalin 2 modulates the cellular response to amyloid beta.

S D Mesquita, A C Ferreira, A M Falcao, J C Sousa, T G Oliveira, M Correia-Neves, N Sousa, F Marques, J A Palha

Index: Cell Death Differ. 21(10) , 1588-99, (2014)

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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.