Oxidative Stress in Health and Disease

Abstract

Oxidative stress, resulting from the excessive intracellular accumulation of reactive oxygen species (ROS), reactive nitrogen species (RNS), and other free radical species, contributes to the onset and progression of various diseases, including diabetes, obesity, diabetic nephropathy, diabetic neuropathy, and neurological diseases, such as Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD). Oxidative stress is also implicated in cardiovascular disease and cancer. Exacerbated oxidative stress leads to the accelerated formation of advanced glycation end products (AGEs), a complex mixture of crosslinked proteins and protein modifications. Relatively high levels of AGEs are generated in diabetes, obesity, AD, and other I neurological diseases. AGEs such as Ne-carboxymethyllysine (CML) serve as markers for disease progression. AGEs, through interaction with receptors for advanced glycation end products (RAGE), initiate a cascade of deleterious signaling events to form inflammatory cytokines, and thereby further exacerbate oxidative stress in a vicious cycle. AGE inhibitors, AGE breakers, and RAGE inhibitors are therefore potential therapeutic agents for multiple diseases, including diabetes and AD. The complexity of the AGEs and the lack of well-established mechanisms for AGE formation are largely responsible for the lack of effective therapeutics targeting oxidative stress and AGE-related diseases. This review addresses the role of oxidative stress in the pathogenesis of AGE-related chronic diseases, including diabetes and neurological disorders, and recent progress in the development of therapeutics based on antioxidants, AGE breakers and RAGE inhibitors. Furthermore, this review outlines therapeutic strategies based on single-atom nanozymes that attenuate oxidative stress through the sequestering of reactive oxygen species (ROS) and reactive nitrogen species (RNS).

Ergothioneine Prevents Neuronal Cell Death Caused by the Neurotoxin 6-Hydroxydopamine

“…These previous studies support our proposition that ergothioneine, which can inhibit excessive ROS production or oxidative stress, may be a way to prevent the development and exacerbation of PD. Furthermore, as oxidative stress is a cause of the onset and exacerbation of various diseases, such as other neurological diseases and diabetes [41,42], it is expected that ergothioneine can be applied as a preventive method for other diseases.…”

Exploring Influence of Production Area and Harvest Time on Specialized Metabolite Content of Glycyrrhiza glabra Leaves and Evaluation of Antioxidant and Anti-Aging Properties

“…Oxidative stress, resulting from the excessive intracellular accumulation of reactive oxygen species (ROS), reactive nitrogen species (RNS), and other free radical species, contributes to the onset and progression of various diseases, among which is Parkinson's disease (PD) [47]. Based on results of the in vitro antioxidant capacity of G. glabra leaves and its main specialized metabolites and in order to estimate the ability of GGL extracts to exert an antioxidant response at the cellular level, not just their radical scavenging capacity, the antioxidant effect of the GGL extracts was evaluated on a yeast model of Saccharomyces cerevisiae expressing human α-synuclein.…”

Methylglyoxal and Advanced Glycation End Products (AGEs): Targets for the Prevention and Treatment of Diabetes-Associated Bladder Dysfunction?

“…RAGE plays an important role in the innate immune response and as a mediator of proinflammatory processes, triggering multiple intracellular signaling pathways, including the generation of proinflammatory mediators such as IL-1β, VCAM-1, and TNF-α via the transcription factor NF-κB [138] and phosphorylation of JNK and p38MAPK [141]. Furthermore, many of the RAGE actions have been attributed to the activation of NADPH oxidase [142], which leads to excess formation of ROS, thus contributing to generate a pro-oxidant environment [143][144][145]. Figure 1 illustrates the MGO-AGEs-RAGE signaling and glyoxalase system (Glo1 and Glo2 enzymes).…”