Abstract
Parkinson's disease (PD) is a common and complex neurodegenerative disease; the pathogenesis of which is still uncertain. Exosomes, nanosized extracellular vesicles, have been suggested to participate in the pathogenesis of PD, but their role is unknown. Here, a metabolomic analysis of serum and brain exosomes showed differentially expressed metabolites between 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride- (MPTP-) induced PD mice and control mice, such as oxidized lipids, vitamins, and cholesterol. These metabolites were enriched in coenzyme, nicotinamide, and amino acid pathways related to PD, and they could be served as preclinical biomarkers. We further found that blood-derived exosomes from healthy volunteers alleviated impaired motor coordination in MPTP-treated mice. Results from immunohistochemistry and western blotting indicated that the loss of dopaminergic neurons in substantia nigra and striatum of PD model mice was rescued by the exosome treatment. The exosome treatment also restored the homeostasis of oxidative stress, neuroinflammation, and cell apoptosis in the model mice. These results suggest that exosomes are important mediators for PD pathogenesis, and exosomes are promising targets for the diagnosis and treatment of PD.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disease, affecting approximately 1% of the population aged > 60 years [1, 2]
A total of 433 metabolites were detected in four groups: serum control (Sc), serum MPTP (Sm), brain control (Bc), and brain MPTP (Bm)
The metabolic data were analyzed according to the OPLS−DA model, and the Scores OPLS−DA Plot was drawn to illustrate the previous differences in each component
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disease, affecting approximately 1% of the population aged > 60 years [1, 2]. The crucial pathological feature of PD is the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), a reduction in dopamine content in the striatum (Cpu), and the appearance of Lewy bodies [5, 6], which are aggregated by abnormally folded α-synuclein. In the early stages of diseases, astrocytes and microglia are both involved in the clearance of extracellular debris or release of nutrients and anti-inflammatory factors, which might aid the survival of neurons [11, 12]. Prolonged overactivation of microglia will exacerbate the death of dopaminergic neurons in the nigra [15, 16]. Studies of young PD patients have revealed that elevated oxidative stress is an important trait of the early disease stages and occurs before severe neuronal loss [18]. The smallest extracellular vesicles (diameter range 50-150 nm), are released by the fusion of multivesicular endosomal bodies with the plasma membrane [19, 20]
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