Aluminum alters cell viability and axonal transport system in Alzheimer's disease pathogenic mutation‐bearing cells

Abstract

AbstractBackground: We previously reported that pulse exposure of cultured rat neurons to aluminum‐maltol resulted in an abnormal distribution of both neurofilament‐L (NF‐L) and fast axonal transported proteins. It was also found that the presenilin 1 (PS1) missense mutation and aluminum affected early neuronal development of the mouse brain. It has been reported that the presenilin (PS) mutation alters neurite outgrowth, and the axonal transport of the amyloid precursor protein (APP)/PS complex is mediated by kinesin. The present study hypothesizes that aluminum might modulate axonal transport and neurite outgrowth in APP/PS mutant‐bearing cells.Methods: We treated SH‐SY5Y cells and HEK293 cells bearing FAD mutations with aluminum‐maltol (Al‐mal) (0, 250 µm, 500 µm, 1 mm, 2 mm) for 1 h, followed by propidium iodide (PI) and Calcein‐AM staining, live and dead assay, double staining of NF‐L/synaptophysin or APP/JNK interacting protein‐1 (JIP‐1) 3 days after treatment.Results: Apoptosis was induced Al‐mal treatment in a dose‐dependent manner in all cell lines. In SH‐SY5Y cells bearing PS1 mutations, there were no differences in the rate of cell viability, except for morphological changes observed by Calcein‐AM staining. The distribution of NF‐L and synaptophysin was modified by PS1 mutations and aluminum, suggesting that the PS mutation induces neuronal dysfunction by disturbance of the axonal transport system. The APP mutation‐bearing cell lines showed significant induction of apoptosis compared to that of wild‐type cells. Oxidative stress might thus influence cell viability in APP mutation‐bearing cells. Enhancement of JIP‐1 staining may reflect a disturbance of the intracellular axonal transport system, as well as compensation due to apoptotic changes.Conclusion: The present results, when taken together, show that aluminum alters cell viability and the axonal transport system in FAD pathogenic mutation‐bearing cells.