Olive leaf-derived exosome-like vesicles attenuate neurotoxicity in an in vitro rotenone model of Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease primarily characterized by dopaminergic neuronal loss, oxidative stress, mitochondrial dysfunction, and protein aggregation. Despite extensive research, current therapeutic options remain limited to symptomatic management, underscoring the need for neuroprotective strategies targeting disease pathology. In this study, we investigated the neuroprotective potential of exosome-like vesicles derived from olive (Olea europaea) leaves (Ole-ELVs) in an in vitro PD model induced by rotenone in SH-SY5Y human neuroblastoma cells. To evaluate the protective impact of olive leaf-derived ELVs, oxidative stress, cell viability, mitochondrial function, and protein aggregation were assessed by measuring reactive oxygen species (ROS) levels, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, JC-1 mitochondrial membrane potential staining, and Thioflavin S staining for α-synuclein aggregation. Our findings indicate that treatment with Ole-ELVs significantly attenuated rotenone-induced ROS production, preserved mitochondrial membrane potential, and reduced protein aggregation. Collectively, these results suggest that Ole-ELVs exert neuroprotective effects through antioxidative, protection against cytotoxicity, and mitochondrial-stabilizing mechanisms, offering a promising natural nanoscale therapeutic candidate for PD.