Transcription factor NRF2 as a promising therapeutic target for Alzheimer’s disease

Oxidative stress is considered as one of the pathogenesis of Alzheimer’s disease (AD) and plays an important role in the occurrence and development of AD. Nuclear factor erythroid 2 related factor 2 (NRF2) is a key regulatory of oxidative stress defence. There is growing evidence indicating the relationship between NRF2 and AD. NRF2 activation mitigates multiple pathogenic processes involved in AD by upregulating antioxidative defense, inhibiting neuroinflammation, improving mitochondrial function, maintaining proteostasis, and inhibiting ferroptosis. In addition, several NRF2 activators are currently being evaluated as AD therapeutic agents in clinical trials. Thus, targeting NRF2 has been the focus of a new strategy for prevention and treatment of AD. In this review, the role of NRF2 in AD and the NRF2 activators advanced into clinical and preclinical studies will be summarized. • NRF2 is regulated by multiple mechanisms. • NRF2 plays a critical role in the pathogenesis of AD. • NRF2 modulates oxidative stress, neuroinflammation, proteostasis, mitochondrial function, and ferroptosis in AD. • Targeting NRF2 is a promising strategy to treat AD.