Reactive Oxygen Comes of Age: Mechanism-Based Therapy of Diabetic End-Organ Damage. (May 2019)

• Record Type: Journal Article
• Authors: Elbatreek, Mahmoud H.; Pachado, Mayra P.; Cuadrado, Antonio; Jandeleit-Dahm, Karin; Schmidt, Harald H.H.W.
• Is Part Of: Trends in endocrinology and metabolism. Volume 30:Number 5(2019)
• Page Start: 312
• Page End: 327
• Publication Date: 2019-05
• Subjects: ROS -- NADPH oxidases -- NRF2 -- network pharmacology -- mechanism-based therapies; Endocrinology -- Periodicals; Metabolism -- Periodicals; Metabolism; 616.4
• DOI: 10.1016/j.tem.2019.02.006
• Languages: English
• ISSNs: 1043-2760

Abstract

Abstract : Reactive oxygen species (ROS) have been mainly viewed as unwanted by-products of cellular metabolism, oxidative stress, a sign of a cellular redox imbalance, and potential disease mechanisms, such as in diabetes mellitus (DM). Antioxidant therapies, however, have failed to provide clinical benefit. This paradox can be explained by recent discoveries that ROS have mainly essential signaling and metabolic functions and evolutionally conserved physiological enzymatic sources. Disease can occur when ROS accumulate in nonphysiological concentrations, locations, or forms. By focusing on disease-relevant sources and targets of ROS, and leaving ROS physiology intact, precise therapeutic interventions are now possible and are entering clinical trials. Their outcomes are likely to profoundly change our concepts of ROS in DM and in medicine in general. Highlights: Lack of comprehensive understanding of DM and its complications, together with its increasing prevalence, represent a major unmet medical need. There is quite a lot known about its mechanisms, but more is needed. Reactive oxygen species (ROS) may hold the answer to this need, but long-standing misconceptions about oxidative stress and the inefficacy of antioxidants have prevented clinical breakthroughs. A new understanding of ROS as both essential signaling molecules and pathomechanism have led to the identification, at different stages of diabetes, of different therapeutically relevant sources and targets of ROS. Network pharmacology and precision diagnostics, currently in advanced stages of clinical development, in conjunction with essential lifestyle changes, will revolutionize the therapy and prevention of diabetes and its end-organ damage.