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
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