The Molecular Mechanism of miRNA-195-5p Regulating ERK Involvement in Abnormal Phosphorylation of Tau Protein by Aluminum Maltol in PC12 Cells.

Although aluminum is ubiquitously present on Earth, it is not necessary for life. Aluminum is a metal element that can induce neurotoxicity. The neurotoxicity of aluminum is mainly caused by the aggregation of abnormally phosphorylated tau protein to form neurofibrillary tangles (NFTs). The phosphorylation of tau is regulated by both kinases and phosphatases. ERK is involved in PHF-type tau hyperphosphorylation. Recent studies have revealed that the interaction between microRNAs (miRNAs) and the ERK/MAPK cascade is related to maintaining the normal function of the nervous system. miR-195 is involved in the early development of AD with a potential impact on cognition. Therefore, we speculate that miRNA-195 may regulate ERK activity, thereby causing hyperphosphorylation of tau protein and neurotoxicity. The purpose of this study was to explore the role of miRNA-195-5p in regulating ERK in the process of aluminum maltol-induced tau hyperphosphorylation. The results showed that aluminum exposure decreased the expression level of miRNA-195-5p and increased the expression of P-ERK, abnormal phosphorylated tau. After inhibiting the activity of ERK, the expression of phosphorylation tau protein decreased. There is an interaction effect between inhibiting the activity of ERK and aluminum exposure on the expression of phosphorylated tau proteins. After the overexpression of miRNA-195-5p, the activity of ERK was inhibited. There is an interaction effect between miRNA-195-5p and aluminum exposure on the expression of phosphorylated tau. In conclusion, miRNA-195-5p regulates ERK involvement in the abnormal phosphorylation of tau protein by Al (mal)3in PC12 cells.