Lipocalin 2 modulates the cellular response to amyloid beta
Autor: | Joana Almeida Palha, Tiago Gil Oliveira, Margarida Correia-Neves, Sandro Da Mesquita, Fernanda Marques, João Carlos Sousa, Ana Mendanha Falcão, Ana C. Ferreira, Nuno Sousa |
---|---|
Přispěvatelé: | Universidade do Minho |
Rok vydání: | 2014 |
Předmět: |
Lipocalin
Amyloid beta-Protein Precursor Mice 0302 clinical medicine Amyloid precursor protein Cells Cultured Neurons Oncogene Proteins 0303 health sciences Bcl-2-Like Protein 11 biology Microglia P3 peptide Acute-phase protein Lipocalins 3. Good health Cell biology medicine.anatomical_structure medicine.symptom Alzheimer's disease Amyloid beta Iron Inflammation 03 medical and health sciences Lipocalin-2 Alzheimer Disease Proto-Oncogene Proteins medicine Animals Molecular Biology 030304 developmental biology Original Paper Amyloid beta-Peptides Science & Technology Membrane Proteins Epithelial Cells Cell Biology medicine.disease Molecular biology Rats Mice Inbred C57BL Astrocytes Heme Oxygenase (Decyclizing) biology.protein Apoptosis Regulatory Proteins 030217 neurology & neurosurgery Acute-Phase Proteins |
Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
ISSN: | 1476-5403 1350-9047 |
Popis: | The production, accumulation and aggregation of amyloid beta (Aß) 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 Aß aggregation. Herein, we describe that lipocalin 2 (LCN2), a mammalian acute-phase protein involved in iron homeostasis, is highly produced in response to Aß1-42 by choroid plexus epithelial cells and astrocytes, but not by microglia or neurons. Although Aß1-42 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 Aß toxicity to astrocytes requires LCN2, which represents a novel mechanism to target when addressing AD.Cell Death and Differentiation advance online publication, 23 May 2014; doi:10.1038/cdd.2014.68. We thank Dr. Ioannis Sotiropoulos for reagents and comments. Sandro Da Mesquita and Ana Catarina Ferreira are recipients of PhD fellowships and Fernanda Marques is recipient of a postdoctoral fellowship by the Fundacao para a Ciencia e Tecnologia (FCT, Portugal)/FEDER. This work was supported by a grant from FCT/FEDER (EXPL/NEUOSD/2196/2013). |
Databáze: | OpenAIRE |
Externí odkaz: |