Exosome-Based Modulation of Ferroptosis in Neurological Disorders: Mechanisms, Therapeutic Potential, and Translational Challenges

Xiaoying Bao¹Liwei Chen¹Hong Yu¹Yunan Xie²Liangxiao Luo¹Li Luo³Hanbing Wang⁴Rongbing Chen⁵Yongwei Cheng²Da Sun^6*Chunwu Zhang^1*

• ¹The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
• ²Wenzhou Medical University, Wenzhou, China
• ³Yiwu Central Hospital, Yiwu, China
• ⁴The University of Hong Kong, Hong Kong, Hong Kong, SAR China
• ⁵City University of Hong Kong, Hong Kong, Hong Kong, SAR China
• ⁶Wenzhou University, Wenzhou, China

Neurological disorders, including acute insults such as stroke and traumatic brain injury and chronic neurodegenerative diseases like Alzheimer's disease and Parkinson's disease, exert a profound global health burden. Ferroptosis, a distinct form of regulated cell death driven by iron accumulation, lipid peroxidation, and oxidative stress, has emerged as a central pathological mechanism across these conditions. Exosomes, nanoscale extracellular vesicles capable of crossing the blood-brain barrier and delivering functional cargos such as microRNAs, long non-coding RNAs, and proteins, have demonstrated remarkable potential in modulating ferroptotic signaling. Through regulation of the GPX4–GSH axis, ferritinophagy, iron homeostasis, and antioxidant pathways, exosome-based interventions offer neuroprotective benefits in diverse models of neurological injury. This review synthesizes current advances in the mechanistic understanding of ferroptosis and highlights emerging strategies leveraging exosomes as precision delivery platforms for ferroptosis-targeted therapy. We also discuss the translational challenges and future directions necessary to realize exosome-guided neuroprotection as a viable clinical paradigm.