Therapeutic potential of the activators of the nuclear factor erythroid 2-related factor 2-antioxidant response element pathway in brain disorders

Oxidative stress is recognized as an important mediator of brain disorders. Nevertheless, there are few antioxidants approved for brain diseases. There are two types of mechanisms as antioxidant systems in vivo, antioxidants and antioxidant enzymes. Antioxidants are consumed by the reaction with reactive oxygen species. Thus, it is important to maintain high concentrations at the requisite site. On the other hand, antioxidant capacity is maintained for around a half-day to one day once antioxidant enzymes are induced. Therefore, low molecular-weight compounds that could induce antioxidant enzymes are considered to be suitable for the treatment and prevention of brain diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway is known as a system for inducing these antioxidant enzymes. Here, the potential for low molecular-weight compounds capable of activating the Nrf2-ARE pathway to become therapeutic agents for brain diseases is discussed.