Oxidative Stress, Neuroinflammation, and Neurodegeneration

Abstract

Oxidative stress and chronic neuroinflammation are two intertwined key pathologic factors in brain aging and neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases. As physiological signaling molecules, reactive oxygen species (ROS) play important roles in many biological processes. However, when excessive amounts of ROS overwhelm the antioxidant defense system, the resultant redox imbalance disrupts cellular integrity and functions. The brain is highly sensitive to oxidative stress. The failure of free radical-scavenging antioxidants in clinical trials demands new therapeutic strategies to block the major sources of oxidative stress in neurodegenerative diseases. While the mitochondrial electron transport chain is the major source of intracellular ROS, over-activated phagocytic NADPH oxidase (NOX2)—the major inflammatory oxidative enzyme—has been demonstrated as a prime mediator of chronic neurodegeneration in models of neurodegenerative diseases. Moreover, emerging evidence has suggested that dysregulated chronic neuroinflammation might be a driving force of decades-long neurodegenerative processes. Blockage of the crossroad of neuroinflammation and oxidative stress may have greater efficacy in the treatment for neurodegenerative diseases. Thus, targeting microglial NOX2 might become a disease-modifying therapeutic strategy for neurodegenerative diseases.