Activation of Nrf2/ARE pathway alleviates the cognitive deficits in PS1V97L‐Tg mouse model of Alzheimer’s disease through modulation of oxidative stress

• DOI: 10.1002/jnr.24357
• Publication Date: 2018-11-21T13:37:20Z
• Authors: Yuanruhua Tian; Wei Wang; Lingzhi Xu; Haitao Li; Yiping Wei; Qiaoqi Wu; Jianping Jia
• Keywords: Neurons; 0301 basic medicine; Amyloid beta-Peptides; Cell Survival; NF-E2-Related Factor 2; Brain; Membrane Proteins; Mice, Transgenic; beta-Transducin Repeat-Containing Proteins; Antioxidant Response Elements; 3. Good health; Mice, Inbred C57BL; Mice; Oxidative Stress; 03 medical and health sciences; Cognition; Alzheimer Disease; NAD(P)H Dehydrogenase (Quinone); Animals; Cognitive Dysfunction; Maze Learning; Heme Oxygenase-1

AbstractOxidative stress refers to an imbalance between oxidative and antioxidative systems due to environmental factors. Although oxidative stress is implicated in the pathogenesis of Alzheimer's disease (AD), its precise role is not yet understood. We aimed to investigate the pathogenic mechanisms of the oxidative stress by using in vitro cultured neurons and in vivo AD models of PS1V97L‐transgenic (Tg) mice. Our results showed that when oxidative stress became increasingly evident, the endogenous protective pathway of nuclear factor E2‐related factor 2 (Nrf2)/antioxidant response element (ARE) decreased in 10‐month‐old PS1V97L‐Tg mice. Activating the Nrf2/ARE pathway suppressed oxidative stress, decreased amyloid‐β (Aβ), and improved the cognitive function of the PS1V97L‐Tg mice. In contrast, blocking the Nrf2/ARE pathway augmented oxidative injury and decreased the cell viability of PS1V97L‐Tg neurons. Our results highlight the role of the Nrf2/ARE pathway in regulating oxidative stress of the PS1V97L‐Tg mice and may indicate a potential therapeutic avenue for AD treatment.