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Early effects of aluminum chloride on beta-secretase mRNA expression in a neuronal model of ß-amyloid toxicity

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Abstract

Amyloid ß peptide (Aß), generated by proteolytic cleavage of the amyloid precursor protein (APP), plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). The key step in the generation of Aß is cleavage of APP by ß-secretases (beta-site APP-cleaving enzyme 1 (BACE1) and BACE2). There has been suggestion of interaction between aluminum and several AD-associated pathways. However, the underlying mechanisms still remain unclear. Here, we report the effects of aluminum chloride (AlCl3) in Aß-induced toxicity using differentiated neuronal SH-SY5Y cells. The metal significantly enhances Aß-induced cell death at concentrations ranging from 50 to 300 µM after 24 and 48 h. After 72 and 96 h treatment, cell death is increased already at 10 µM. Early coexposure of cells to 10 µM AlCl3 and 2 µM Aß differentially affected ß-secretase mRNA levels as compared to single Aß treatment after 1 and 3 h. BACE1 levels were slightly reduced after 1 h and significantly increased after 3 h exposure, whereas BACE2 levels were increased at both times considered. Both genes’ mRNA levels were downregulated at longer times (6, 12, and 24 h). Although these results indicate that aluminum toxicity is correlated to changes in both BACE1 and BACE2 expression levels, the subsequent common downregulation observed suggests that aluminum involvement in the Aß cascade is subtle, and other underlying mechanisms might be involved.

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Acknowledgements

We thank Mr. P. Asero for his technical support and Mrs. F. Capilli for her administrative support. This work was partially granted with funds from “National Institute for Occupational Safety and Prevention” (ISPESL, Italy)—grant no. 533F/X1.

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Authors and Affiliations

  1. Department of Anatomy, Diagnostic Pathology, Legal Medicine, Hygiene and Public Health, University of Catania, Via S. Sofia, 87, 95123, Catania, Italy

    Alessandro Castorina, Adriana Tiralongo, Salvatore Giunta, Maria Luisa Carnazza & Velia D’Agata

  2. Department of Health Sciences, University of Molise, Campobasso, Italy

    Giovanni Scapagnini

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  1. Alessandro Castorina
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  2. Adriana Tiralongo
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  3. Salvatore Giunta
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  4. Maria Luisa Carnazza
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  6. Velia D’Agata
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Correspondence to Velia D’Agata.

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Castorina, A., Tiralongo, A., Giunta, S. et al. Early effects of aluminum chloride on beta-secretase mRNA expression in a neuronal model of ß-amyloid toxicity. Cell Biol Toxicol 26, 367–377 (2010). https://doi.org/10.1007/s10565-009-9149-3

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