Introduction: Alzheimer disease (AD) is the most common age-related neurodegenerative disease characterized by extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles containing hyper-phosphorylated tau. As an important molecule in the pathogenesis of AD, Aβ interferes with multiple aspects of mitochondrial function, including energy metabolism failure, production of reactive oxygen species (ROS) and permeability transition pore formation. Recent studies have demonstrated that Aβ progressively accumulates within mitochondrial matrix and provides a direct link to mitochondrial toxicity. Convincing evidence demonstrates mitochondria as a crucial organel in ROS generation and links oxidative stress to the development of neuronal dysfunction and death, which suggests a key pathogenic role for oxidative stress in AD. In this review, we focus on changes in mitochondrial defects and oxidative stress in the pathogenesis of AD. Interaction of AD with Aβ exaggerates Aβ-mediated mitochondrial and neuronal perturbation, leading to impaired synaptic function and memory. Conclusion: Blockade of ROS generation may be a potential therapeutic strategy for treatment of AD.

Introduction: There is an increasing prevalence of Alzheimer's disease (AD). Amyloid-beta deposition and neurotoxicity play an effective role in AD. Oxidative stress is thought to be central in the pathogenesis that leads to production of reactive oxygen species and causing damages of the macromolecules in target cells. It has been reported that the nuclear factor erythroid 2 related factor 2 (Nrf2) is a key regulator of endogenous inducible defense systems in the body and increase the level of many antioxidants, including glutathione-s-transferase. Under oxidative damage conditions, Nrf2 translocates to the nucleus, binds to the antioxidant response element (ARE), and enhances sequence to initiate transcription of cytoprotective genes. This review focuses on cellular mechanisms of Nrf2 regulation and discusses the relationship between Nrf2 regulation and AD. Conclusion: In general, we suggest that Nrf2-ARE activation is a novel neuroprotective pathway that can be consider as a promising therapeutic strategy for the treatment of neurodegenerative disorders, such as AD.