Extracellular particles: emerging insights into central nervous system diseases.

Extracellular particles (EPs), including extracellular vesicles (EVs) and non-vesicular extracellular particles (NVEPs), are multimolecular biomaterials released by cells that play a crucial role in intercellular communication. Recently, new subtypes of EPs associated with central nervous system (CNS), such as exophers and supermeres have been identified. These EPs provide new perspectives for understanding the pathological progression of CNS disorders and confer potential diagnostic value for liquid biopsies in neurodegenerative diseases (NDs). Moreover, EPs have emerged as promising drug delivery vehicles and targeted platforms for CNS-specific therapies. In this review, we delineate the landscape of EP subtypes and their roles in the pathophysiology of CNS diseases. We also review the recent advances of EP-based diagnosis in NDs and highlight the importance of analytical platforms with single-particle resolution in the exploitation of potential biomarkers. Furthermore, we summarize the application of engineered EVs in the treatment of CNS diseases and outline the underexplored potential of NVEPs as novel therapeutic agents.