Aluminum inhibits non-amyloid pathways via retinoic acid receptor.

Abstract Background Aluminium neurotoxicity has been widely confirmed and mainly manifests as cognitive impairment. Al3+ can inhibit the expression of ADAM10, a key enzyme of the nonamyloid pathway, but its mechanism of toxicity has not been fully elucidated. Studies have shown that RARs can regulate ADAM10 expression. Methods We explored whether Al3+ affects the expression of ADAM10 through RARs, thereby affecting the nonamyloid pathway. Results Al3+ reduced the expressions of RARα, RARβ and ADAM10. The expression levels of the RARα, RARβ and ADAM10 proteins were upregulated in the RA group compared with the control group. In the RA + 200 μmol Al(mal)3 group, the downregulation of RARα, RARβ and ADAM10 was weaker than that of the 200 μmol Al(mal)3 group, which indicated that RA participated in and upregulated the expression of ADAM10 through RARα and RARβ. Conclusion Al3+ inhibits ADAM10 expression through RARα and RARβ and results in a decrease in the nonamyloid pathway.