Exploring the role of exosomes in diabetic neuropathy: From molecular mechanisms to therapeutic potential

Abstract

Diabetic neuropathy (DN) is a debilitating complication of diabetes mellitus (DM), characterized by progressive neuronal damage, sensory dysfunction, and impaired quality of life. Recent advances in exosome research have elucidated their crucial role in DN's pathogenesis, diagnosis, and treatment. Exosomes-nanoscale extracellular vesicles-function as vehicles for molecular cargo, including microRNAs (miRNAs), proteins, and lipids, which mediate intercellular communication and regulate key biological processes. Pathologically, hyperglycemia and hyperlipidemia induce the release of exosomes enriched with pathogenic miRNAs, such as miR-130a and miR-20b-3p, which disrupt neuronal function, axonal regeneration, and inflammatory pathways. Conversely, diagnostic studies highlight the utility of exosomal biomarkers like miR-7 and miR-221 in the early detection and monitoring of DN. Therapeutically, Schwann cell-derived and mesenchymal stromal cell (MSC)-derived exosomes demonstrate neuroprotective and reparative effects by enhancing mitochondrial function, modulating inflammation, and promoting axonal repair. Emerging approaches, including engineered exosomes and miRNA-enriched vesicles, further expand their therapeutic potential. Despite these advances, challenges such as standardization, large-scale production, and clinical validation remain in translating these findings into clinical practice. This review underscores the multifaceted roles of exosomes in DN and highlights their potential as innovative tools for precision diagnostics and targeted therapies, paving the way for future research and clinical applications.