Oxidative Stress and its Implications for Future Treatments and Management of Alzheimer Disease.

Oxidative imbalance is one of the earliest manifestations of Alzheimer disease (AD) actually preceding the classic pathology of amyloid ß deposits and neurofibrillary tangles. Clinical trials examining antioxidant modulation by a number of global interventions show efficacy, while simple supplementation has limited benefit suggesting complexity of multiple contributing factors. In this review, we highlight new insights regarding novel approaches to understanding and treating AD based on holistic views of oxidative balance including diet.

Role of mitochondrial-mediated signaling pathways in Alzheimer disease and hypoxia.

Development of effective treatments for Alzheimer's disease is complicated by the poor understanding of its pathophysiology. Recent work suggests mitochondria may play a primary role in neurodegeneration, due to alterations in mitochondria turnover and that the brain is specifically susceptible, due to high energy demand. Mitochondria are the major source of cellular energy through oxidative phosphorylation and regulate intracellular calcium levels and survival pathways. Hypoxia has been implicated in several neurodegenerative diseases including Alzheimer's disease. During hypoxic events, mitochondrial complex III produces high levels of reactive oxygen species (ROS). These ROS seem to have a primary role in the regulation of the transcription factor hypoxia inducible factor 1alpha that triggers death effectors. Here we discuss the role of mitochondria in AD putting focus on the activation of hypoxia-mediated mitochondrial pathways, which could eventually lead to cell degeneration and death.