Redox signaling at the crossroads of human health and disease

Abstract

Redox biology is at the core of life sciences, accompanied by the close correlation of redox processes with biological activities. Redox homeostasis is a prerequisite for human health, in which the physiological levels of nonradical reactive oxygen species (ROS) function as the primary second messengers to modulate physiological redox signaling by orchestrating multiple redox sensors. However, excessive ROS accumulation, termed oxidative stress (OS), leads to biomolecule damage and subsequent occurrence of various diseases such as type 2 diabetes, atherosclerosis, and cancer. Herein, starting with the evolution of redox biology, we reveal the roles of ROS as multifaceted physiological modulators to mediate redox signaling and sustain redox homeostasis. In addition, we also emphasize the detailed OS mechanisms involved in the initiation and development of several important diseases. ROS as a double‐edged sword in disease progression suggest two different therapeutic strategies to treat redox‐relevant diseases, in which targeting ROS sources and redox‐related effectors to manipulate redox homeostasis will largely promote precision medicine. Therefore, a comprehensive understanding of the redox signaling networks under physiological and pathological conditions will facilitate the development of redox medicine and benefit patients with redox‐relevant diseases.

OGG1 Inhibition Reduces Acinar Cell Injury in a Mouse Model of Acute Pancreatitis

“…Whereas ROS and RNS-induced direct and cumulative cell damage is an attractive concept to explain tissue injury in inflammation and ischemia-reperfusion injury of vital organs, recently novel signaling mechanisms have also been put forward to serve as underlying pathways of these ROS and RNS-related pathologies [ 40 , 41 ]. Moreover, some of these pathways also explain how ROS and RNS contribute to the inflammatory pathways.…”

Flavonols and Flavones as Potential anti-Inflammatory, Antioxidant, and Antibacterial Compounds

“…An increase in reactive species levels occurs with aging and the development of diseases, including cancer, Parkinson's disease, diabetes, and cardiovascular diseases [ 77 ]. ROS increase is linked to different diseases, reviewed by [ 78 ]. For instance, excessive ROS accumulation leads to glutathionylation modification and proteasomal degradation of MAP kinase phosphatase-1, which prevents insulin signaling.…”

“…Furthermore, phosphorylated tau protein and A β are risk factors in Alzheimer's disease, which originate from the downregulated Nrf2 and increased ROS burden. Finally, extracellular and intracellular ROS activate TGF- β signaling triggering the epithelial-mesenchymal transition of epithelial cells and survival of circulating tumor cells during cancer metastasis [ 78 ].…”

“…The enzymatic system comprises antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). In the nonenzymatic antioxidant system, glutathione (GSH); ascorbate (AsA); numerous simple [78].…”

The Hidden Notes of Redox Balance in Neurodegenerative Diseases

“…Historically, ROS were recognized as detrimental molecules capable of reacting non-specifically with proteins, lipids and nucleic acids and generating other reactive species, potentially contributing to maladaptive responses and to harmful outcomes. Indeed, when the sophisticated antioxidant systems cannot handle the increased production of free radicals, oxidative stress occurs [ 6 ]. However, depending on the tissue environment, cell type and status, the generated ROS may also act as signaling molecules and take part in orchestrating multiple cellular biological processes [ 7 , 8 ].…”