Peroxiredoxin-Mediated Redox Regulation in Neurons: From Neurite Development to Degeneration.

In the nervous system, reactive oxygen species (ROS) serve essential roles in intracellular signaling, but their dysregulation can impair neuronal function and survival. Peroxiredoxins (Prdxs) have classically been regarded as antioxidant enzymes that scavenge peroxides, yet a growing body of evidence indicates that their roles in the brain extend beyond ROS removal. They are increasingly recognized as regulators of redox-dependent processes with isoform-specific roles. In this review, we discuss the functions of Prdxs in the brain from a broad cellular perspective, focusing on their roles in neuronal differentiation, mitochondrial and endoplasmic reticulum (ER) homeostasis, and major neurological disorders including Alzheimer's disease, Parkinson's disease, and ischemic stroke. Prdx isoforms show distinct condition-dependent functions regulated by localization, regulatory state, and cellular environment. Collectively, a broader view of Prdxs as dynamic modulators of neural cell biology may help us understand their coordinated integrate their roles in the coordinated regulation of redox-sensitive cellular processes. Clarifying the isoform-specific and cell-type-specific dependent mechanisms underlying their function will be essential in defining the roles of Prdxs in brain physiology and diseases and to evaluating their therapeutic potential.