Therapeutic Approaches to Alzheimer's Disease Through Modulation of NRF2.

The nuclear factor erythroid-derived 2-related factor 2 (NFE2L2/NRF2) is a master transcription factor that regulates oxidative stress-related genes containing the antioxidant response element (ARE) in their promoters. The damaged function and altered localization of NRF2 are found in most neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis. These neurodegenerative diseases developed from various risk factors such as accumulated oxidative stress and genetic and environmental elements. NRF2 activation protects our bodies from detrimental stress by upregulating antioxidative defense pathway, inhibiting inflammation, and maintaining protein homeostasis. NRF2 has emerged as a new therapeutic target in AD. Indeed, recent studies revealed that NRF2 activators have therapeutic effects in AD animal models and in cultured human cells that express AD pathology. This review will focus on the NRF2 pathway and the role of NRF2 in AD and suggest some NRF2 inducers as therapeutic agents for AD.