The role of exosomes as oligonucleotide delivery system for managing α-synuclein in Parkinson's disease: A systematic review of in vivo studies.

Although Parkinson's disease (PD) is primarily idiopathic, genetic mutations-accounting for approximately 5%-15% of cases with regional variability-have prompted the development of gene expression modulators, such as oligonucleotides, to target and reduce alpha-synuclein (α-syn) accumulation. However, challenges in delivering these agents to the brain have limited their therapeutic potential. This study systematically reviews the use of exosomes as delivery systems for oligonucleotides aimed at reducing α-syn aggregation in PD. A comprehensive literature search was conducted using Scopus, Embase, OVID, and ISI Web of Science databases up to January 2022, targeting in vivo studies relevant to the subject. Of 904 initial records, five eligible studies were selected. Three utilized transgenic mouse models and two used induced models to simulate PD. All reported a reduction in α-syn aggregation in the midbrain-particularly in the substantia nigra-following treatment with exosome-delivered oligonucleotides. This reduction was associated with decreased neuronal death and improved motor function. No significant toxicity or immune response was reported. Exosome-mediated oligonucleotide delivery appears to be a promising approach to reduce α-syn aggregation, protect dopaminergic neurons, and improve motor symptoms in animal models of PD.