Neuroprotective effect of NSCs-derived extracellular vesicles in Parkinson's disease models

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms, caused by the degeneration and loss of dopaminergic neurons in the substantia nigra. Current therapies are limited to symptom management, unable to prevent neuronal loss or halt the progression of the disease. A significant limitation to more effective treatments is the difficulty of crossing the blood-brain barrier (BBB). Extracellular vesicles (EVs) communication plays a crucial role in several physiological processes within the nervous system. Notably, EVs have the unique ability to cross the BBB, making them a highly promising vehicle for delivering therapeutic agents directly to the brain. Given the rising prevalence of PD, the need for therapies that prevent neuronal death and promote cell survival is urgent. This study explores the potential of neural stem cell-derived extracellular vesicles (NSC-EVs) using two in vitro models of PD. Our findings demonstrate that NSC-EVs significantly enhance the survival of dopaminergic neurons by reducing apoptosis and showing strong neuroprotective effects. Notably, the natural extracellular vesicles used in this study are enriched with Catalase, a potent scavenger protein with antioxidant properties. This natural enrichment further strengthens their neuroprotective capacity, enabling them to mitigate oxidative stress and protect vulnerable neurons. The use of such naturally enriched extracellular vesicles represents a promising approach for developing innovative therapies to effectively combat Parkinson’s disease.