Lipocalin 2 modulates the cellular response to amyloid beta.
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.
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.
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Mesquita
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.
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Ferreira
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.
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Falcao
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.
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Sousa
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.
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Oliveira
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.
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Correia-Neves
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.
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Sousa
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.
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Marques
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.
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D000209:Acute-Phase Proteins / Q000235:genetics*; D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis*; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis; D007249:Inflammation / Q000276:immunology; D007501:Iron / Q000378:metabolism; D000071068:Lipocalin-2; D054834:Lipocalins / Q000096:biosynthesis* / Q000235:genetics*; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D051381:Rats
D000209:Acute-Phase Proteins; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; C000606778:Bcl2l11 protein, rat; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D008565:Membrane Proteins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; C071332:Lcn2 protein, mouse; D007501:Iron; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat