The Opposing Roles of miR-۲۰۰a and miR-۳۴a in Modulating the Nrf۲/Keap۱ Pathway in Alzheimer's Disease

Dysregulation of the Nrf۲/Keap۱ antioxidant pathway is a critical contributor to the oxidative stress prevalent in Alzheimer's disease (AD). Emerging evidence highlights microRNAs (miRNAs) as key modulators of this pathway. This review delineates the opposing roles of two pivotal miRNAs: miR-۲۰۰a, which promotes Nrf۲ activation by directly targeting and suppressing Keap۱, and miR-۳۴a, which undermines cellular defenses by repressing Nrf۲ expression. The resultant imbalance—diminished miR-۲۰۰a and elevated miR-۳۴a—likely exacerbates oxidative damage, neuroinflammation, and neuronal loss in AD. Restoring redox homeostasis through miRNA-based strategies, such as miR-۲۰۰a mimics or miR-۳۴a inhibitors, presents a promising therapeutic avenue. Further investigation into this miRNA-Nrf۲ axis is essential for developing targeted interventions against AD progression. This study aims to elucidate the opposing roles of miR-۲۰۰a and miR-۳۴a in modulating the Nrf۲/Keap۱ pathway in Alzheimer's disease.

کلیدواژه ها:

Alzheimer's disease ، Nrf۲/Keap۱ pathway ، oxidative stress ، microRNA ، miR-۲۰۰a ، miR-۳۴a