Nrf2 as a Potential Therapeutic Target for Traumatic Brain Injury

In this review, we discuss the possibility and feasibility of nuclear factor erythroid 2-related factor 2 (Nrf2) as a therapeutic target to minimize the devastating effects of a brain injury. To complete this review, comprehensive literature searches were conducted in MEDLINE, PubMed, Embase, and PsycINFO databases for English scientific peer-reviewed articles through December 2022. This short review addressed the different sources of oxidative stress and its effects on blood-brain barrier (BBB) dysfunction, mitochondrial damage, and changes in a variety of inflammatory molecules associated with central nervous system (CNS) injury. At last, we explained the potential efficacy of the Nrf2 transcription factor in reducing oxidative stress-mediated secondary damages after a CNS injury. The role of CPUY192018, an inhibitor of Nrf2-Keap1 protein-protein interaction in protecting the injured brain cells is given as evidence of Nrf2's role in activating antioxidant genes. Overall, the scope of Nrf2 in developing therapeutic interventions for a variety of pathophysiological conditions associated with CNS injury-induced free radical/inflammatory signaling is acknowledged. Nrf2 has a widespread application in basic and clinical neuroscience for understanding and treating free radical/inflammatory signaling disorders, including neurological diseases. The development of innovative therapeutic strategies using Nrf2-inducing agents can be applied to reduce the complications of TBI before advancing it to posttraumatic stress disorder (PTSD).

Automated summary

This review discusses the potential and feasibility of using nuclear factor erythroid 2-related factor 2 (Nrf2) as a therapeutic target to minimize the devastating effects of brain injury. The review summarizes the different sources of oxidative stress and their impact on blood-brain barrier dysfunction, mitochondrial damage, and changes in various inflammatory molecules associated with central nervous system injury. The potential effectiveness of the Nrf2 transcription factor in reducing oxidative stress-mediated secondary damage after CNS injury is explained, and evidence of Nrf2's role in activating antioxidant genes is provided. The review recognizes the scope of Nrf2 in developing therapeutic interventions for various pathophysiological conditions associated with CNS injury-induced free radical/inflammatory signaling. Nrf2 has widespread applications in basic and clinical neuroscience for understanding and treating disorders related to free radical/inflammatory signaling, including neurological diseases.