Abstract
The limited regenerative capacity of the central nervous system (CNS) severely hinders treatment of neurodegenerative and neuroinflammatory diseases. These conditions, frequently exacerbated by aging, share common hallmarks such as neuroinflammation, demyelination, and neuronal loss. While neural stem cells (NSCs) hold great therapeutic promise due to their paracrine effects, including extracellular vesicle (EV) release, direct transplantation presents significant challenges. This review focuses on NSC-derived EVs as a novel therapeutic strategy, as we explore their multimodal mechanisms in modulating neuroinflammation, promoting neurogenesis, and restoring cellular bioenergetics through the delivery of bioactive molecules and mitochondrial transfer. Recent advances in NSC-EV-based therapies for age-associated neurodegenerative diseases are highlighted, along with key challenges in EV production, preservation, and targeted delivery. Finally, we outline future directions for translating this promising approach into effective clinical treatments.