摘要Myocyte enhancer factor 2C(MEF2C)is highly expressed in the nervous system,and regulates neuro-development,synaptic plasticity,and inflammation.However,its mechanism in Alzheimer's disease(AD)is underestimated.In this study,the role and mechanism of MEF2C were investigated in the brain tissue specimens from patients with AD,APPswe/PSEN1dE9 double transgenic(APP/PS1_DT)mice,and SH-SY5Y cells treated with β-amyloid peptide(Aβ).The results indicated that the expression of MEF2C is significantly reduced,and the expression of MEF2C/Aβ in different parts of brain is negatively correlated in patients with AD.Knockdown of MEF2C promotes cell apoptosis and the level of β-amyloid precursor protein cleaving enzyme 1(BACE)but reduces BACE2 expression.In addition,knockdown of Mef2c enhances the generation and aggregation of Aβ in the cortex of APP/PS1_DT mice,reduces the expression of synaptic proteins,exacerbates the ability of learning and memory of APP/PS1_DT mice,damages the structure of mitochondria,increases the oxidative stress(OS)level,and inhibits the expression levels of members of the Nrf2-ARE signal pathway.In summary,inhibition of MEF2C exacerbates the toxic effect of Aβ in vivo and in vitro,damages synaptic plasticity,reduces the ability of learning and memory of APP/PS1 mice,and increases the level of OS via the Nrf2-ARE signal pathway.