From Bench to Brain: Translating EV and Nanocarrier Research into Parkinson's Disease Therapies.

Parkinson's disease (PD) is a disabling neurodegenerative disorder that is defined by progressive loss of dopaminergic neurons in the substantia nigra, deposition of α-synuclein aggregates, and chronic neuroinflammation. While symptomatic therapies have evolved, disease-modifying therapies remain elusive. Extracellular vesicles (EVs), particularly those derived from mesenchymal stem cells (MSC-EVs), have emerged as promising therapeutic agents because they possess a natural ability to cross the blood-brain barrier and deliver bioactive cargo. Herein, we review the dual-edged function of EVs in PD pathogenesis: facilitating the transfer of toxic α-synuclein while also conferring neuroprotective signals through MSC-EVs. We outline the mechanisms of MSC-EV-mediated neuroprotection that include the regulation of oxidative stress, neuroinflammation, and autophagy. We also emphasize new nanocarrier systems designed to bypass delivery challenges in PD therapy. While preclinical studies are extremely encouraging, significant issues regarding scalability, standardization, and clinical translation must be resolved before realizing the ultimate therapeutic potential of EV-based and nanocarrier-based approaches to PD.