Inflammatory and Oxidative Pathways Driving Multisystem Disease Progression

Abstract

Modern epidemic of non-communicable chronic diseases requires changes in paradigm of the classical pattern of single-organ pathology to the model of systemic network dysfunction. The key to this change lies in the fact that chronic inflammation and oxidative stress are not secondary events but the primary and linked cause of systemic disease. They create a vicious cycle where inflammatory signaling triggers enzymes such as NADPH oxidase and mitochondrial disruption which releases reactive oxygen species (ROS); which in turn activate major inflammatory pathways such as NF-kB and NLRP3 inflammasome and oxidative damage produces molecules that sustain immune activation. It is a molecular nexus that is a universal pathological mechanism, which destroys the functioning of organ systems. It pushes endothelial dysfunction in atherosclerosis, stimulates insulin resistance in diabetes, promotes neuroinflammation in neurodegenerative diseases, and propagates dysfunction across, such as the gut-liver-brain axis. The systemic production of inflammatory cytokines and oxidized metabolites perpetuates the cycle and the processes like cellular senescence institutionalize it. Thus, chronic diseases can be interpreted as symptoms of some common underlying condition- the existence of dysregulated circuitry in the system. This redefinition requires an abandonment of an organ-focused approach to the treatment of inflammatory-oxidative loop as the root cause of disease and instead governs treatment with the goal of restoring homeostasis to the entire body circuitry.