Cdk5 Inhibition and Aβ42 Increase Bace1 Level in Primary Neurons by a Post- Transcriptional Mechanism: Implications of Cdk5 as a Therapeutic Target for Alzheimer’s Disease*
نویسندگان
چکیده
Background: β-secretase BACE1 is elevated in Alzheimer’s disease (AD) during pathogenesis though an unknown mechanism. Result: Aβ42 increases BACE1 in primary neurons via a post-transcriptional mechanism and is synergized by Cdk5 inhibitors. Conclusion: Aβ42 increases neuronal BACE1 translation through a Cdk5-independent pathway. Significance: Amyloid may initiate a feedforward mechanism of BACE1 elevation and Aβ production in AD and Cdk5 inhibitor drugs may exacerbate this.
منابع مشابه
Transcriptional Regulation of β-Secretase by p25/cdk5 Leads to Enhanced Amyloidogenic Processing
Cyclin-dependent kinase 5 (cdk5) has been implicated in Alzheimer's disease (AD) 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 (STAT1/3) was identified in the BACE1 promoter. STA...
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