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

Abstract

Aluminum (Al) is a common neurotoxic element that can exacerbate intracellular β-amyloid (Aβ) deposition. Reelin is a highly conserved extracellular glycoprotein that is involved in intracellular Aβ deposition. However, the action of Reelin on aluminum-induced Aβ deposition is not fully understood. Here, we investigated the effects of the Reelin-Dab1 signaling pathway on Aβ 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 Aβ₄₂, and decreased expression of Aβ₄₀. 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 Aβ₄₀ 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 Aβ₄₀ 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 Aβ deposition. Thus, our findings provided important evidence to better understand how the Reelin-Dab1 signaling pathway may be a potential mechanism of Aβ deposition induced by aluminum.