Biology, Pathology, and Targeted Therapy of Exosomal Cargoes in Parkinson's Disease: Advances and Challenges.

Parkinson's disease (PD) involves the loss of dopamine neurons and accumulation of alpha-synuclein (α-syn), leading to Lewy bodies. While α-syn-targeting immunotherapies show promise, clinical application is challenging. Emerging strategies include nano-platforms for targeted delivery and imaging, and cell-based therapies with patient-specific dopaminergic neurons, aiming to enhance treatment effectiveness despite challenges. Exosome-based methodologies are emerging as a promising area of research in PD due to their role in the spread of α-syn pathology. Exosomes are small extracellular vesicles that can carry misfolded α-syn and transfer it between cells, contributing to the progression of PD. They can be isolated from biological fluids such as blood and cerebrospinal fluid, making them valuable biomarkers for the disease. Additionally, engineering exosomes to deliver therapeutic agents, including small molecules, RNA, or proteins, offers a novel approach for targeted therapy, capitalizing on their natural ability to cross the blood-brain barrier (BBB). Ongoing studies are evaluating the safety and efficacy of these engineered exosomes in clinical settings. This review explores the role of exosomes in PD, focusing on their potential for diagnosis, treatment, and understanding of pathology. It highlights advancements and future directions in using exosomes as biomarkers and therapeutic tools.