Exosome-mediated delivery of Parkin rescues mitochondrial dysfunction in Parkinson's disease models
Parkinson\'s disease (PD) is the second most common neurodegenerative disorder, caused by a reduction of dopamine release in the midbrain. Parkin (PRKN; also known as PARK2) is an E3 ubiquitin ligase that regulates mitochondrial quality. Mutations in the Parkin gene are associated with early-onset autosomal recessive PD, characterized by mitochondrial dysfunction. Recent studies have suggested the potential therapeutic use of Parkin delivery for the treatment of PD. We have developed to deliver Parkin protein with engineered extracellular vesicles to rescue mitochondrial dysfunction.In our study, we utilized photocleavable proteins, which can be cleaved upon exposure to light of a specific wavelength. By strategically placing the photocleavable protein between Parkin and the exosomal membrane protein, we observed the light-induced release of Parkin into exosomes through cleavage of the photocleavable protein.We evaluated to assess the effectiveness of Parkin exosomes in removing damaged mitochondria and alleviating oxidative stress, thus rescuing mitochondrial dysfunction in Parkinson\'s disease models.
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