Role of the PKA-PGC1α-BACE1 Signaling Pathway in Aluminum-Induced Neurotoxicity in PC12 Cells

This objective of this study was to investigate how aluminum affects the PKA-PGC1α-BACE1 pathway in PC12 cells and its role in neurotoxicity.

According to the exposure dose of aluminum maltol, PC12 cells were selected for research and divided into five experimental groups and six intervention groups. After 24 h of 8-Bromo-cAMP intervention, they were treated with Al-(mal)₃ for 24 h. After the experiment, cell morphology was observed, and the cell survival rate was assessed using the Cell Counting Kit-8 (CCK-8) assay. Western blot and ELISA techniques were used to detect the expression of relevant proteins, enzyme activity, and Aβ levels.

Under the microscope, the number of cells in the aluminum maltol group decreased, the morphology changed, and the number of intercellular connections decreased. However, after treatment with the 8-Bromo-cAMP agonist, a significant increase in the number of cells was observed, and significant morphological changes occurred, with a gradual increase in intercellular connections. CCK-8 assays showed that cell viability gradually decreased with increasing aluminum exposure doses. Western blot showed that PKA and PGC1α expressions decreased with higher aluminum doses, while BACE1 increased; agonist treatment upregulated PGC1α and downregulated BACE1, with minimal effect on PKA; and ELISA results indicated that aluminum reduced PKA enzyme activity but increased BACE1 activity and Aβ levels.

Exposure to aluminum inhibits the PKA-PGC1α-BACE1 signaling pathway, while PKA agonists can alleviate neurotoxicity by restoring this pathway.