Fig. 1

The integrative role of extracerebral-derived EVs in neurodegenerative disease pathogenesis and therapy. Extracerebral-derived EVs, originating from diverse peripheral sources such as bone, adipose tissue, and gut microbiota, are depicted as pivotal entities in the intercommunication between the periphery and the CNS. These vesicles possess the remarkable ability to traverse the systemic circulation, penetrate the BBB, and deliver molecular cargo that can influence NDD mechanisms. Additionally, the inherent biological characteristics of EVs present them as promising vectors for targeted therapeutic delivery to the CNS, offering a novel approach to treat NDDs. Engineered EVs, optimized for CNS targeting, could represent a paradigm shift in the modulation of pathogenic processes underlying NDDs and the administration of therapeutic agents