Effect of the Reelin-Dab1 signaling pathway on the abnormal metabolism of Aβ protein induced by aluminum

Aluminum (Al) is a common neurotoxic element that can exacerbate intracellular beta-amyloid (A beta) deposition. Reelin is a highly conserved extracellular glycoprotein that is involved in intracellular A beta deposition. However, the action of Reelin on aluminum-induced A beta deposition is not fully understood. Here, we investigated the effects of the Reelin-Dab1 signaling pathway on A beta deposition in aluminum maltol (Al(mal)(3)) exposure in rat pheochromocytoma-derived cells (PC12). Our results showed that Al(mal)(3) exposure decreased activity of PC12, increased expression of A beta(42), and decreased expression of A beta(40). Moreover, Al(mal)(3) exposure in PC12 induced Reelin-Dab1 signaling pathway-associated proteins changed, decreased expression of Reelin and Dab1, and increased expression of pdab1. Moreover, the expression of Reelin, Dab1, and A beta(40) was found to be elevated in PC12 exposed to Al(mal)(3) and corticosterone compared to those exposed to Al(mal)(3). Also, the expression of Reelin, Dab1, and A beta(40) was found to be depressed in PC12 exposed to Al(mal)(3) and streptozotocin compared with cells exposed to Al(mal)(3) alone. These results suggested that Al(mal)(3) inhibits the expression of the Reelin-Dab1 signaling pathway, promoting A beta deposition. Thus, our findings provided important evidence to better understand how the Reelin-Dab1 signaling pathway may be a potential mechanism of A beta deposition induced by aluminum.

Automated summary

Aluminum is a neurotoxic element that can worsen the deposition of intracellular beta-amyloid (Aβ). This study explored the effects of the Reelin-Dab1 signaling pathway on Aβ deposition in rats exposed to aluminum maltol. The results showed that aluminum exposure reduced cell activity, increased the expression of Aβ(42), and decreased the expression of Aβ(40). Furthermore, aluminum exposure altered the expression of proteins associated with the Reelin-Dab1 signaling pathway. These findings provide important evidence for understanding the potential mechanism of aluminum-induced Aβ deposition through the Reelin-Dab1 signaling pathway.