The effect of BACE1-AS on ß-amyloid generation by regulating BACE1 mRNA expression.

ABSTRACT

BACKGROUND: The BACE1 antisense transcript (BACE1-AS) is a conserved long noncoding RNA (lncRNA). The level of BACE1-AS is significantly increased and the level of the BACE1 mRNA is slightly increased in subjects with AD. BACE1-AS exerts a significant moderating effect on the expression of the BACE1 mRNA and promotes the formation of Aß. After the administration of Aß1-42 to SH-SY5Y cells and C57/BL6J mice, we detected the expression of BACE1-AS, BACE1 mRNA, and BACE1 protein, as well as the concentration of Aß1-40. Then, we silenced the expression of BACE1-AS in SH-SY5Y and 20E2 cells using siRNAs targeting BACE1-AS and detected its effects on the levels of the BACE1 mRNA and BACE1 protein and Aß1-40 generation. RESULTS: The administration of Aß1-42 increased the expression of BACE1-AS, BACE1 mRNA and protein, as well as the concentration of Aß1-40 in SH-SY5Y cells and the brains of C57BL/6J mice. Pretreatment with the BACE1-AS siRNA inhibited the effect of Aß1-42 on increasing the expression of BACE1-AS and BACE1, as well as the generation of Aß. CONCLUSIONS: The mechanism by which exogenous Aß1-42 induces BACE1 expression and Aß generation is mediated by BACE1-AS. BACE1-AS is involved in the mechanism regulating BACE1 expression and Aß generation in APPsw transgenic cells.