Nrf2 Signaling Pathway: a Potential Therapeutic Target in Combating Oxidative Stress and Neurotoxicity in Chemotherapy-Induced Cognitive Impairment.

Chemotherapy-induced cognitive impairment (CICI) is one of the major adverse effects of antineoplastic drugs, which decrease the quality of life in cancer survivors. Extensive experimental and clinical research suggests that chemotherapeutic drugs generate an enormous amount of reactive oxygen species (ROS), contributing to oxidative stress, neuroinflammation, blood-brain barrier (BBB) disruption, and neuronal death, eventually leading to CICI. Despite the progress in exploring different pathological mechanisms of CICI, effective treatment to prevent CICI progression has not been developed yet. Nrf2 is the principal transcription factor that regulates cellular redox balance and inflammation-related gene expression. Emerging evidence suggests that upregulation of Nrf2 and its target genes could suppress oxidative stress, and neuroinflammation, restore BBB integrity, and increase neurogenesis. This review discusses the role of Nrf2 in CICI, how it responds to oxidative stress, inflammation, neurotoxicity, and potential Nrf2 activators that could be used to enhance Nrf2 activation in CICI.