细胞内bmal1和cbp蛋白水平的振荡表达被减弱.ppt

Aβ-induced degradation of BMAL1 and CBP leads to circadian rhythm disruption in Alzheimer’s disease Molecular Neurodegeneration (19 March 2015；IF= 6.563；PMID 王宁 2015.10.8 IMI CONFIDENTIAL Background * Aβ, Amyloid-beta SCN, Suprachiasmatic nucleus CBP, Creb-binding protein Per2, Period circadian protein homolog 2 BMAL1, Aryl hydrocarbon receptor nuclear translocator-like 生理节律相关的蛋白，时钟基因： IMI CONFIDENTIAL Materials and Methods * Animal : 5XFAD mice (APP/PSEN1) AD小鼠 APP K670N/M671L+I716V+V717I PSEN1 M146L+L286V Cell: HT22 mouse hippocampal cells, Cos7 monkey kidney cells Methods: Behavioral assay, Immunocytochemistry, Western blot, real-time PCR, Immunoprecipitation, Luciferase reporter assays, BiFC assay, ELISA. IMI CONFIDENTIAL Results * 1. Abnormal circadian behavior in 5XFAD mice IMI CONFIDENTIAL Results * 1. Abnormal circadian behavior in 5XFAD mice IMI CONFIDENTIAL Results * 2. The expression of molecular circadian clock genes, Bmal1, Cbp and Per2, are impaired in 5XFAD mice 与对照小鼠相比，AD小鼠SCN中Bmal1, Per2, Cbp mRNA水平明显发生了改变。 IMI CONFIDENTIAL Results * 2. The expression of molecular circadian clock genes, Bmal1, Cbp and Per2, are impaired in 5XFAD mice IMI CONFIDENTIAL Results * 2. The expression of molecular circadian clock genes, Bmal1, Cbp and Per2, are impaired in 5XFAD mice 与对照小鼠相比，AD小鼠SCN中Bmal1, Per2, Cbp 蛋白水平并不呈现振荡表达。 IMI CONFIDENTIAL Results * 3. Aβ induces the degradation of BMAL1 and CBP Aβ作用之后，细胞内 BMAL1和CBP蛋白水平的振荡表达被减弱。 IMI CONFIDENTIAL Results * 3. Aβ induces the degradation of BMAL1 and CBP IMI CONFIDENTIAL Results * 3. Aβ induces the degradation of BMAL1 and CBP Aβ作用24 h之后，细胞内 BMAL1和CBP蛋白水平的振荡表达被减弱。 IMI CONFIDENTIAL Results * 3. Aβ induces the degradation of BMAL1 and CBP Aβ作用24 h之后，细胞内 BMAL1和CBP蛋白的相互作用被减弱。 IMI CONFIDENTIAL Results * 4. The degradation of BMAL1 by Aβ involves the sumoylation of BMAL1 随着Aβ作用时间的增长，细胞内 BMAL1蛋白的水平逐渐降低。 IMI CONFIDENTIAL Results * 4. The degradation of BMAL1 by Aβ