Abstract
Deposition and dysfunction of U1 small nuclear ribonucleoprotein (snRNP) have been revealed in Alzheimer's disease (AD), but whether U1 is involved in the amyloid precursor protein (APP) and Tau pathways remains unclear. Here, we investigate this by inhibiting the U1 components in cultured cells and examining the expression changes of AD-related genes to these two canonic pathways. We find that knockdown of U1-70K and U1C increases the protein expressions of APP and GSK-3β while reduces that of Nicastrin in a dose-dependent manner. Knockdown of U1A shows no effects on the expression of these proteins. The real-time PCR results show that the mRNA expression levels of APP, Nicastrin and GSK-3β are unchanged, decreased, and increased, respectively. In addition, U1-70K knockdown suppresses Tau phosphorylation and causes altered splicing of Tau exon 10. This study suggests that the effect of U1 snRNP knockdown is component-specific and more likely involved in APP deregulation in AD.