| First Author | Qin X | Year | 2016 |
| Journal | J Biol Chem | Volume | 291 |
| Issue | 42 | Pages | 22276-22287 |
| PubMed ID | 27576688 | Mgi Jnum | J:237285 |
| Mgi Id | MGI:5811943 | Doi | 10.1074/jbc.M116.738849 |
| Citation | Qin X, et al. (2016) Early Growth Response 1 (Egr-1) Is a Transcriptional Activator of beta-Secretase 1 (BACE-1) in the Brain. J Biol Chem 291(42):22276-22287 |
| abstractText | Accumulation of amyloid-beta peptide (Abeta) in the brain is regarded as central to Alzheimer's disease (AD) pathogenesis. Abeta is generated by a sequential cleavage of amyloid precursor protein (APP) by beta-secretase 1 (BACE-1) followed by gamma-secretase. BACE-1 cleavage of APP is the committed step in Abeta synthesis. Understanding the mechanism by which BACE-1 is activated leading to Abeta synthesis in the brain can provide better understanding of AD pathology and help to develop novel therapies. In this study, we found that the levels of Abeta and BACE-1 are significantly reduced in the brains of mice lacking transcription factor early growth response 1 (Egr-1) when compared with the WT. We demonstrate that in COS-7 cells, Egr-1 binds to the BACE-1 promoter and activates BACE-1 transcription. In rat hippocampal primary neurons, overexpression of Egr-1 induces BACE-1 expression, activates BACE-1, promotes amyloidogenic APP processing, and enhances Abeta synthesis. In mouse hippocampal primary neurons, knockdown of BACE-1 almost completely blocks Egr-1-induced amyloidogenic APP processing and Abeta synthesis. Our data indicate that Egr-1 promotes Abeta synthesis via transcriptional activation of BACE-1 and suggest that Egr-1 plays role in activation of BACE-1 and acceleration of Abeta synthesis in AD brain. Egr-1 is a potential therapeutic target for AD. |
