AUTHOR=Zhang Cuilin , Tan Zhenqiu , Xie Yongzhuang , Zhao Yingjun , Huang Timothy Y. , Lu Zhaoping , Luo Hong , Can Dan , Xu Huaxi , Zhang Yun-wu , Zhang Xian 

TITLE=Appoptosin Mediates Lesions Induced by Oxidative Stress Through the JNK-FoxO1 Pathway

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=11

YEAR=2019

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2019.00243

DOI=10.3389/fnagi.2019.00243

ISSN=1663-4365

ABSTRACT=<p>Oxidative stress is a common feature of neurodegenerative diseases and plays an important role in disease progression. Appoptosin is a pro-apoptotic protein that contributes to the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and progressive supranuclear palsy. However, whether appoptosin mediates oxidative stress-induced neurotoxicity has yet to be determined. Here, we observe that appoptosin protein levels are induced by hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) exposure through the inhibition of proteasomal appoptosin degradation. Furthermore, we demonstrate that overexpression of appoptosin induces apoptosis through the JNK-FoxO1 pathway. Importantly, knockdown of appoptosin can ameliorate H<sub>2</sub>O<sub>2</sub>-induced JNK activation and apoptosis in primary neurons. Thus, we propose that appoptosin functions as an upstream regulator of the JNK-FoxO1 pathway, contributing to cell death in response to oxidative stress during neurodegeneration.</p>