Yuan Wen

Cyclin-dependent kinase 5 has been implicated in Alzheimer's disease pathogenesis. Here, we demonstrate that overexpression of p25, an activator of cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A p25/cdk5 responsive region containing multiple sites for signal transducer and activator of transcription was identified in the BACE1 promoter. STAT3 interacts with the BACE1 promoter, and p25-overexpressing mice had elevated levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels. Furthermore, mice with a targeted mutation in the STAT3 cdk5 responsive site had lower levels of BACE1. Increased BACE levels in p25 overexpressing mice correlated with enhanced amyloidogenic processing that could be reversed by a cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis

Based on the strict definitions of concepts, such as deduction, the deduction rule and the deduction system, the form axiom, the substantive axiom, this article clearly shows the essence of the deductive reasoning, namely “Related attribute and the related restriction relations, which are conveyed in what the main concept of the deduction refers to, must be contained in those conveyed in what the premise proposition refers to”。Then puts forward the theorem “contradiction can not be derived from the strict deduction system”, and gives the proofs.