Melatonin-loaded MSCs-derived exosomes as therapeutic carriers to alleviate levodopa-induced dyskinesia in Parkinson's disease.

Parkinson's disease (PD) causes dopaminergic neuron damage in substantia nigra, with levodopa-induced dyskinesia (LID) as a side effect of long-term treatment with levodopa. Exosomes (Exo) from mesenchymal stem cells (MSC) are getting attention as nanosized carriers which facilitate the transfer of drugs through the blood-brain barrier. This study examined Melatonin-loaded Exo (MltExo) for neuroprotective effects in LID models of PD. MltExo was characterized for size, stability, and drug release. In vitro studies demonstrated improved cell viability, proliferation, reduced apoptosis, and ROS production when exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and levodopa. In vivo, experiments with mice showed that MltExo treatment protected against behavioral changes and locomotor deficits, enhancing cognitive function in LID group. Due to their antioxidant properties, MltExo preserved SNc, TH+, and nissl-stained cells. It reduced the inflammatory cytokines IL-1β and TNF-α at mRNA level. These findings suggest that MltExo is a promising therapeutic carrier for reducing LID in PD.