Exosomes as a Double-Edged Sword in Neurodegenerative Diseases: Roles and Engineering Strategies

Central nervous system (CNS) disorders, particularly neurodegenerative diseases such as Alzheimers disease (AD) and Parkinsons disease (PD), represent major challenges in contemporary medical research. The bloodbrain barrier (BBB), an essential protective interface of the CNS, helps maintain brain homeostasis but also restricts the entry of most drugs and therapeutic molecules into the brain, severely limiting clinical efficacy. As nanoscale extracellular vesicles, exosomes possess an intrinsic capacity to traverse biological barriersincluding the BBBand can transport a wide range of bioactive cargos to modulate various physiological and pathological processes. Research indicates that exosomes play pivotal roles in the pathological progression of neurodegenerative diseases: they can mediate the spread of pathogenic proteins while also contributing protective effects such as the clearance of pathological aggregates and the attenuation of neuroinflammation. Moreover, engineering strategies (e.g., drug loading and targeted surface modification) expand the potential of exosomes as drug-delivery vehicles. Despite promising diagnostic and therapeutic prospects, challenges including exosomal heterogeneity, limited loading efficiency, imperfect targeting specificity, and stability in clinical settings remain significant bottlenecks. With further advances in exosome engineering, standardized characterization, and scalable production, exosomes hold promise as important tools for the early diagnosis and precision treatment of neurodegenerative diseases.