Down-regulation of the expression of Pax6 through Aβ insults in Alzheimer’s disease cell model

Abstract

Alzheimer’s disease (AD) is one of the major neurodegenerative diseases that seriously affect the central nervous system (CNS). It features progressive loss of memory, linguistic competence, mobility and coordination, as well as great change in personality. Due to its dynamic disease progression, there are no perfect biomarkers till now. As aging becomes a worldwide issue, a quality life of the senile people calls for early diagnosis, efficient cure and better prognosis of this distracting disease. Though scientists are still struggling in the marsh, trying to figure out any clues to explain the relationship between Alzheimer’s disease and amyloid/tau hypothesis, microglia steps onto the stage for its important role as phagocytic cells in the CNS. Now it’s almost a common sense that neurodegeneration diseases are closely related with dysfunctional clearance of dead cells and neuroinflammation. Thus, the receptors expressed by microglia become hot spot. In the present study, I firstly localized the intracellular expression of Pax6 and found out that in the natural case it was universally distributed with a higher expression level in the nucleus. But when overexpressed, it seemed that the protein products intended to retain within the nucleus. Then, I constructed one Pax6 knock-down stable cell line and one Pax6 transiently overexpressed cell line and the expression levels of five target genes (TREM2, GAS6, CD36, ANXA1 and MFG-E8) screened from previous studies were measured using qRT-PCR (quantitative reverse transcription polymerase chain reaction) respectively. The data showed a significant correspondence between Pax6 and TREM2 which indicated a probable intermediate regulatory role of Pax6 on TREM2. These results confirmed Pax6 to be a DNA-binding transcription factor and extended the mechanism behind its deteriorative role as it could down-regulate the expression of TREM2, which was recognized as a positive player in AD pathology. Furthermore, the result raised the possibilities that Pax6 could be an effective therapeutic target, and the potential of TREM2 as a novel biomarker.