Extracellular Vesicles and Neuroimmune Crosstalk in Neurological Disorders: Mechanisms and Therapeutic Implications

Neuroinflammation is a hallmark of many neurological disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). Growing evidence indicates that extracellular vesicles (EVs) are key regulators of neuroimmune communication. EVs derived from neurons, microglia, astrocytes, and peripheral immune cells transfer bioactive molecules, including proteins, lipids, and non-coding RNAs (ncRNAs), that modulate synaptic activity, inflammatory signaling, and the spread of pathogenic factors. By directly interacting with CNS cells, EVs exert both pro-inflammatory and anti-inflammatory effects in shaping the neuroinflammatory landscape. This review summarizes advances in EV-mediated neuroimmune crosstalk; highlights microglia–neuron communication and the regulatory roles of ncRNAs carried by EVs; and discusses the therapeutic potential of EV-based approaches and immune-modulating compounds, such as natural polyphenols, in mitigating neuroinflammation. Together, these insights underscore EVs as critical regulators of the CNS immune landscape and promising targets for novel therapeutic strategies.