Authors: Yiyuan Xia, Hiroshi Qadota, Zhi-Hao Wang, Pai Liu, Xia Liu, Karen X. Ye, Courtney J. Matheny, Ken Berglund, Shan Ping Yu, Derek Drake, David A. Bennett, Xiao-Chuan Wang, Bruce A. Yankner, Guy M. Benian, Keqiang Ye
Published: 2022-03-30
Source: Full article
The age-related cognitive decline of normal aging is exacerbated in neurodegenerative diseases including Alzheimer’s disease (AD). However, it remains unclear whether age-related cognitive regulators in AD pathologies contribute to life span. Here, we show that C/EBPβ, an Aβ and inflammatory cytokine–activated transcription factor that promotes AD pathologies via activating asparagine endopeptidase (AEP), mediates longevity in a gene dose–dependent manner in neuronal C/EBPβ transgenic mice. C/EBPβ selectively triggers inhibitory GABAnergic neuronal degeneration by repressing FOXOs and up-regulating AEP, leading to aberrant neural excitation and cognitive dysfunction. Overexpression of CEBP-2 or LGMN-1 (AEP) in