Oxidative stress is one of the pathological mechanisms of Alzheimer's disease (AD), and ferroptosis has been determined to be involved in neurodegenerative diseases such as AD. Senegenin (Sen) prevents oxidative damage in nerve cells via a mechanism that may be highly related to ferroptosis. However, the mechanism of ferroptosis pathway involvement in AD is unclear. In this study, we established a model of PC12 cytotoxic injury induced by A beta(25-35), and we detected the level of oxidative damage, MMP, and ferroptosis-related protein expression. The results showed that, compared with control group, the level of ROS increased, GPX activities decreased, and MDA levels increased in A beta(25-35) group. A beta(25-35) could induce mitochondrial depolarization in PC12 cells and Fer-1 could not reverse this damage. WB revealed that A beta(25-35) group had increased ACSL4 and PEBP1 proteins, and decreased GPX4 protein. After adding Sen in the model, the level of oxidative damage was reduced, and mitochondrial depolarization was reversed compared with A beta(25-35) group. WB suggested that the expression of ACSL4 and PEBP1 proteins decreased, and the expression of GPX4 protein increased by Sen treatment. In conclusion, we found that Sen exhibits strong neuroprotective activity against A beta(25-35) induced oxidative damage and lipid metabolic associated with ferroptosis. Inhibiting nerve cell ferroptosis might facilitate the future development of strategies to AD.
基金：
Natural Science Foundation
of Guangdong province (No. 2014A030313394), the Project of Science
and Technology of Guangzhou (2014J4100098), the Fundamental
Research Funds for the Central Universities in China (No. 21613401),
and the Project of Science and Technology Plan in Guangzhou: City-
University (Hospital) joint funding (202201020016).
第一作者机构：[1]Jinan Univ, Sch Med, Dept Pathophysiol, Key Lab State Adm Tradit Chinese Med, 601 Ave Huangpu West, Guangzhou 510632, Guangdong, Peoples R China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Zhang Heping,Zhou Wei,Li Jianling,et al.Senegenin Rescues PC12 Cells with Oxidative Damage Through Inhibition of Ferroptosis[J].MOLECULAR NEUROBIOLOGY.2022,59(11):6983-6992.doi:10.1007/s12035-022-03014-y.
APA：
Zhang, Heping,Zhou, Wei,Li, Jianling,Qiu, Zhaohui,Wang, Xiaotong...&Qi, Renbin.(2022).Senegenin Rescues PC12 Cells with Oxidative Damage Through Inhibition of Ferroptosis.MOLECULAR NEUROBIOLOGY,59,(11)
MLA：
Zhang, Heping,et al."Senegenin Rescues PC12 Cells with Oxidative Damage Through Inhibition of Ferroptosis".MOLECULAR NEUROBIOLOGY 59..11(2022):6983-6992
