Plant-Derived Exosomes in Neurodegenerative Disorders and Age-Related Brain Dysfunction: From Isolation to Clinical Potential.

INTRODUCTION: Plant-derived Exosome-like Nanovesicles (PELNs) have the potential to exhibit improved biological functions in multiple pathological disorders, particularly in neurodegenerative and age-related brain diseases. In this review, advanced isolation techniques, including Differential Ultracentrifugation (dUC), Size-Exclusion Chromatography (SEC), and Polyethylene Glycol (PEG) precipitation, were systematically evaluated to optimize the structural integrity, purity, and biological activity of PELNs. METHODS: Novel studies on PELNs were the primary focus of this review. Evidence-based studies were compared and discussed in terms of chemical and functional characteristics, as well as optimized production strategies to enhance the therapeutic properties of PELNs. RESULTS: According to the consensus of reviewed studies, PELNs demonstrate efficient cellular uptake due to their lipophilic chemical structures and modulate intracellular signaling pathways related to neurodegeneration. The main drawbacks of PELNs' utilization mostly depend on the extraction methods and limited delivery through the BBB. A combination of optimized methods, such as dUC and SEC, may exhibit maintained therapeutic strategies for neurological applications. DISCUSSION: Due to the limited number of experimental studies in Parkinson's Disease (PD) and Alzheimer's Disease (AD), and brain aging, advances in PELNs extraction methods have been shown to enhance BBB delivery and therapeutic efficacy. Every study claims the superiority of its own method; however, none of these methods fully addresses the limitations inherent in producing optimal results. CONCLUSION: PELNs represent a promising platform for neurological dysfunction and brain aging-related disorders. However, isolation and characterization methods must be carefully optimized and validated to ensure the production of therapeutically active PELNs suitable for BBB delivery.