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Studies have shown that aluminum (Al) is associated with Alzheimer's disease (AD) causality, however, the mechanism underlying this link remains unclear. To investigate the Al neurotoxicity, the high Al-affinity protein from pig hippocampus was screened by native gel electrophoresis and Al3+ plus 8-hydroxyquinoline (8-HQ) staining. The protein with high Al3+ affinity was identified to be 14-3-3ζ, which was then used for raising antibodies. By 8-HQ staining and immunocytochemical localization, we found that the co-location of Al3+ and 14-3-3ζ increased markedly in the Al-exposed rat hippocampus tissue and the cultured rat primary hippocampal neuronal cells. By immune analysis with antibodies against tau, we found that tau accumulation mainly located in the neurons of cornu amonis 3 and dentate gyrus of the rat hippocampus. Total free tau in hippocampus tissue and in neuronal cells increased 26.0% and 20.2%, respectively after Al-exposure. By immunofluorescent staining, we found that the levels of tau and 14-3-3ζ co-location declined 15.9% or 12.1% in the hippocampus tissue or in neuronal cells after Al exposure. These findings indicated that 14-3-3ζ combing with tau can prevent the over phosphorylation of tau and can be disturbed by Al exposure due to Al3+ binding to 14-3-3ζ, which could account for the mechanisms underlying Al neurotoxicity related to AD.

Mechanisms Underlying Aluminum Neurotoxicity Related to 14-3-3ζ Protein