Polydeoxyribonucleotide (PDRN) has emerged as a biologically active nucleic-acid therapeutic with broad applications in dermatology, regenerative medicine, and tissue repair. Although its clinical utility has been recognized across diverse ROS-driven pathological conditions, the underlying molecular signaling mechanisms have remained fragmented. This review integrates and systematizes current findings to reconstruct PDRN’s signaling network within a hierarchical, multilayered framework. Evidence from existing studies indicates that PDRN-mediated activation of the A2A adenosine receptor initiates a coordinated cascade involving cAMP-PKA signaling, MAPK modulation, PI3K-Akt activation, NF-κB suppression, MITF inhibition, and HIF-1α regulation. These pathways collectively converge on the upstream suppression of ROS generated through mitochondrial dysfunction, NOX activation, UV-induced MAPK signaling, and melanogenesis-associated oxidative reactions. Beyond its anti-inflammatory and pro-regenerative properties, PDRN reprograms multiple transcriptional regulators―including CREB, NF-κB, MITF, and HIF-1α—thereby influencing ECM homeostasis, cytokine balance, apoptosis resistance, angiogenesis, and pigmentation. Taken together, current evidence positions PDRN not as a classical antioxidant but as an upstream network regulator that mitigates ROS-driven cellular damage and restores tissue homeostasis. This mechanistic framework provides a rationale for its therapeutic potential in photoaging, wound healing, pigmentary disorders, and ischemic injury, while highlighting future research opportunities involving Nrf2 signaling, NOX isoform specificity, and mitochondrial dynamics.
Jung et al. (2025) studied this question.