Mechanism by Which Aluminum Regulates the Abnormal Phosphorylation of the Tau Protein in Different Cell Lines

Aluminum (Al) is an environmental neurotoxin to which humans are extensively exposed; however, the molecular mechanism of aluminum toxicity is unclear. Several studies have indicated that exposure to aluminum can cause abnormal phosphorylation of the tau protein. The purpose of this study was to investigate respectively the special molecular mechanism of abnormal regulation on synthesis and degradation of the tau protein induced by AlCl₃ in cells of different species. The results of tau protein showed that the sites of abnormal tau phosphorylation induced by AlCl₃ are Thr231, Ser262, and Ser396 in N2a cells. Meanwhile, the expressions of Thr181, Thr231, and Ser262 increased abnormally in SH-SY5Y cells. The result of the study showed that PP2A expression was high in N2a cells, while GSK-3β and PP2A in SH-SY5Y cells were involved in the synthesis process of abnormal tau phosphorylation induced by AlCl₃. In N2a cells, the ubiquitin-proteasome pathway (UPP) mainly regulated tau phosphorylation at Ser262 and Ser396. Meanwhile, in SH-SY5Y cells, the UPP mainly regulated tau phosphorylation at Thr231 and Ser396. In summary, the UPP is involved in the degradation of Tau that is abnormally phosphorylated induced by AlCl₃, but this process is site-specific and differs in cells of different species.