Kalirin as a key mediator of aluminum-induced cognitive dysfunction and neurotoxicity: Integrated evidence from...

Occupational aluminum (Al) exposure is associated with cognitive decline, but the underlying molecular mechanisms remain unclear. This study investigates the role of Kalirin in Al-induced neurotoxicity. A cross-sectional study was conducted in 2019 with 172 workers from a Shanxi aluminum plant. Participants were categorized into high and low Al exposure groups based on plasma aluminum levels, and cognitive function was assessed using the MoCA test. Phosphoproteomic analysis revealed a significant 90 % reduction in Kalirin expression in the high-exposure group compared to the low-exposure group (P < 0.05). Multiple regression analysis demonstrated that Al exposure negatively correlated with Kalirin, GAP43, MAP2 expression, and cognitive function, while Kalirin was positively correlated with these factors (q < 0.05). Bayesian network modeling indicated that decreased Kalirin expression, along with reduced GAP43 and MAP2 levels, increased the risk of cognitive impairment. In vitro, HT22 neurons exposed to aluminum maltolate showed reduced neuronal activity, impaired dendritic development, and disruption of the Kalirin-Rac1 pathway. Overexpression of Kalirin via lentiviral transfection reversed these effects, restoring neuronal integrity (P < 0.05). These findings suggest that Al-induced neurotoxicity involves disruption of the Kalirin pathway, highlighting Kalirin as a potential therapeutic target for mitigating Al-related cognitive dysfunction.