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.