Unveiling Exosomes and Microvesicles in Parkinson's Disease: Mechanistic Insights Into Cell Death Pathways and Therapeutic Potential.

Parkinson's disease (PD) is characterized by progressive neuronal loss driven by dysregulated cell death pathways, yet the precise role of extracellular vesicles (EVs) in mediating these processes remains fragmented. Exosomes, enriched with microRNAs (miRNAs) and proteins like α-synuclein, propagate pathology and modulate neuroprotection, while microvesicles, carrying cytokines, amplify neuroinflammation. We synthesize recent studies to critically analyze the mechanisms, such as the dual role of exosomal miRNAs in oxidative stress and neuroprotection, and address methodological limitations, including EV heterogeneity and model-specific discrepancies. By integrating recent findings on EV subpopulations, such as exosomes versus microvesicles, and their distinct roles in α-synuclein propagation, along with the interplay between neuroinflammation and pyroptosis via nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) inflammasome activation, this review proposes a mechanistic framework for harnessing EVs in PD therapeutics.