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| Content Provider | Springer Nature Link |
|---|---|
| Author | Castorina, Alessandro Tiralongo, Adriana Giunta, Salvatore Carnazza, Maria Luisa Scapagnini, Giovanni D’Agata, Velia |
| Copyright Year | 2010 |
| 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. |
| Starting Page | 367 |
| Ending Page | 377 |
| Page Count | 11 |
| File Format | |
| ISSN | 07422091 |
| Journal | Cell Biology and Toxicology |
| Volume Number | 26 |
| Issue Number | 4 |
| e-ISSN | 15736822 |
| Language | English |
| Publisher | Springer Netherlands |
| Publisher Date | 2010-01-29 |
| Publisher Place | Dordrecht |
| Access Restriction | Subscribed |
| Subject Keyword | Aluminum chloride Alzheimer’s disease BACE1 BACE2 Beta-amyloid Biochemistry Pharmacology/Toxicology Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Health, Toxicology and Mutagenesis Toxicology |
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