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

ABSTRACT

Aluminum (Al) is a common neurotoxic element that can exacerbate intracellular ß-amyloid (Aß) deposition. Reelin is a highly conserved extracellular glycoprotein that is involved in intracellular Aß deposition. However, the action of Reelin on aluminum-induced Aß deposition is not fully understood. Here, we investigated the effects of the Reelin-Dab1 signaling pathway on Aß 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 Aß42, and decreased expression of Aß40. 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 Aß40 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 Aß40 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 Aß deposition. Thus, our findings provided important evidence to better understand how the Reelin-Dab1 signaling pathway may be a potential mechanism of Aß deposition induced by aluminum.