Role of redox signaling in neuroinflammation and neurodegenerative diseases.
Reactive oxygen species (ROS), a redox signal, are produced by various enzymatic reactions and chemical processes, which are essential for many physiological functions and act as second messengers. However, accumulating evidence has implicated the pathogenesis of several human diseases including neurodegenerative disorders related to increased oxidative stress. Under pathological conditions, increasing ROS production can regulate the expression of diverse inflammatory mediators during brain injury. Elevated levels of several proinflammatory factors including cytokines, peptides, pathogenic structures, and peroxidants in the central nervous system (CNS) have been detected in patients with neurodegenerative diseases such as Alzheimer's disease (AD). These proinflammatory factors act as potent stimuli in brain inflammation through upregulation of diverse inflammatory genes, including matrix metalloproteinases (MMPs), cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), and adhesion molecules. To date, the intracellular signaling mechanisms underlying the expression of target proteins regulated by these factors are elusive. In this review, we discuss the mechanisms underlying the intracellular signaling pathways, especially ROS, involved in the expression of several inflammatory proteins induced by proinflammatory factors in brain resident cells. Understanding redox signaling transduction mechanisms involved in the expression of target proteins and genes may provide useful therapeutic strategies for brain injury, inflammation, and neurodegenerative diseases.
Department of Nursing, Division of Basic Medical Sciences, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
Hsi-Lung
HL
Hsieh
Department of Physiology and Pharmacology and Health Aging Research Center, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-San, Taoyuan, Taiwan.
Chuen-Mao
CM
Yang
D001921:Brain / Q000378:metabolism / Q000473:pathology; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
D016207:Cytokines; D017382:Reactive Oxygen Species