Other
13 Authors
- Sandoval IM,
- Jia J,
- Yu SP,
- Sun X,
- Manfredsson FP,
- Gong K,
- Ye K,
- Johnson PF,
- Wang JZ,
- Wang ZH,
- Wei ZZ,
- Zhang Z,
- Liu X
| First Author | Wang ZH | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 1784 |
| PubMed ID | 29725016 | Mgi Jnum | J:262986 |
| Mgi Id | MGI:6161078 | Doi | 10.1038/s41467-018-04120-z |
| Citation | Wang ZH, et al. (2018) C/EBPbeta regulates delta-secretase expression and mediates pathogenesis in mouse models of Alzheimer's disease. Nat Commun 9(1):1784 |
| abstractText | Delta-secretase cleaves both APP and Tau to mediate the formation of amyloid plaques and neurofibrillary tangle in Alzheimer's disease (AD). However, how aging contributes to an increase in delta-secretase expression and AD pathologies remains unclear. Here we show that a CCAAT-enhancer-binding protein (C/EBPbeta), an inflammation-regulated transcription factor, acts as a key age-dependent effector elevating both delta-secretase (AEP) and inflammatory cytokines expression in mediating pathogenesis in AD mouse models. We find that C/EBPbeta regulates delta-secretase transcription and protein levels in an age-dependent manner. Overexpression of C/EBPbeta in young 3xTg mice increases delta-secretase and accelerates the pathological features including cognitive dysfunctions, which is abolished by inactive AEP C189S. Conversely, depletion of C/EBPbeta from old 3xTg or 5XFAD mice diminishes delta-secretase and reduces AD pathologies, leading to amelioration of cognitive impairment in these AD mouse models. Thus, our findings support that C/EBPbeta plays a pivotal role in AD pathogenesis via increasing delta-secretase expression. |
