Multifaceted roles of extracellular vesicles in the interplay of neuroinflammation and neurodegenerative diseases

Despite advances in understanding neurodegenerative disease mechanisms, effective treatments remain elusive. Extracellular vesicles (EVs), key mediators of intercellular communication within the central nervous system (CNS), are increasingly recognized for their involvement in the pathogenesis of neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Huntington's disease (HD). In vivo studies demonstrate EVs' crucial role in maintaining CNS homeostasis, modulating neuroinflammatory responses, and influencing tissue repair and regeneration following injury, thereby impacting disease progression and recovery. Their unique properties, including small size and ability to cross the blood-brain barrier (BBB), position them as promising candidates for both biomarkers and therapeutics in CNS diseases. This review delves into the significant impact of neuroinflammation on neurodegenerative conditions, specifically focusing on the multifaceted contributions of EVs and their intricate interplay with the inflammatory landscape. We explore EV biogenesis, cargo composition, diverse roles in neuroinflammation (including intercellular communication and neuroprotection), their potential as biomarkers and drug delivery vehicles across the BBB for diagnosis or treatment of neuroinflammation implemented neurodegenerative diseases.