Peroxiredoxins in central nervous system: implications for chronic pain and anaesthetic-induced neurotoxicity management

Oxidative stress, an imbalance between the prooxidant-antioxidant system, is regarded as one of the crucial causative pathomechanisms of chronic pain. However, direct scavenging of intracellular reactive oxygen species (ROS) by antioxidants may disrupt normal physiological homeostasis. Peroxiredoxins (Prdxs), a family of ROS-regulating enzymes, have recently aroused growing interest in the broad field of antioxidant research. Six distinct groups of Prdxs (Prdx1-6) have been identified to date. Prdxs are essential for regulating diverse biological processes, including oxidative stress, neuroinflammation, apoptosis, mitochondrial dynamics, endoplasmic reticulum (ER) stress, and synaptic plasticity. Interestingly, the differential expression patterns of Prdxs in central nervous system (CNS) tissues, cell types, and subcellular locations imply specialized functions. This review systematically summarizes the expression patterns of specific Prdxs in tissues and cells of murine and human, as well as the regulatory factors of their enzymatic activities. It also discusses the underlying cellular signaling pathways through which Prdxs participate in several biological processes as well as chronic pain and anaesthetic-induced neurotoxicity. In addition, we summarize the therapeutic potential of Prdxs inducers in CNS disorders based on preclinical studies. A better understanding of these processes can promote the development of novel therapeutic targets for treating chronic pain and anaesthetic-induced neurotoxicity.