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.

Abstract

Redox homeostasis is essential for human health, supported by multiple functional signaling pathways including the Keap1‐Nrf2, FOXO, HIF and NF‐κB pathways. However, redox imbalance causes multiple serious diseases such as type 2 diabetes, atherosclerosis, chronic obstructive pulmonary disease, Alzheimer's disease, cancer, and aging. Our review emphasizes the significance of redox manipulation in clinical therapeutics and points out the existing challenges involved in this field.