Objective: To verify the hypothesis that serum-derived exosomes from patients with Parkinson’s disease (PD) may serve as risk carriers for inter-neuronal risk transmission, eventually resulting in the characteristic symptoms.

Background: Cell-to-cell transport of risk molecules is a highly anticipated pathogenic mechanism in the initiation and progression of various neurodegenerative diseases. Extracellular exosome-mediated neuron to neuron transport of α-synuclein (α-syn) is increasingly recognized as a potential etiologic mechanism in PD. Exosomal inflammation has also been increasingly implicated in PD pathogenesis and could trigger, facilitate, or aggravate disease development. Since exosomes are abundant in circulation, it is unclear whether PD serum exosomes could induce symptomatic onset in vivo.

Method: Exosomes from PD patients and healthy controls were isolated and verified, the content of α-syn was compared by western blotting (WB) and ELISA. Then exosomes were added into the PD cell model to observe their effect on α-syn aggregation. In addition, exosomes were intravenously and intrastriatally injected into the balb/c mouse. The behavioral changes, component of Lewy body such as pathological α-syn, P62, ubiquitin and dopamine content, the inflammatory markers were assessed and analyzed.

Results: Exosomes were confirmed by WB, transmission electron microscopy (TEM) and Nanosight. The content of α-syn, p-syn(ser129) and inflammatory factor such as TNF-α and IL-6 are more abundant in mild to late PD patients. As expected, PD serum exosomes could trigger α-syn, ubiquitin, and P62 aggregation in cell model. More importantly, the intravenous or intrastriatal treatment of mice with exosomes from PD patient serum could evoke protein (α-syn, p-syn(ser129), P62) aggregation, trigger dopamine neuron degeneration, induce microglial activation, and cause apomorphine-coaxed rotation and movement defects (bradykinesia).

Conclusion: We present evidence that the injection of PD serum exosomes into mice initiates a pathological change, including protein aggregation, loss of TH-positive neurons in SN, and impaired motor coordination, thus elucidating the possible role of the exosomes in the pathogenic process of PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/exosomes-from-patients-with-parkinsons-disease-are-pathological-in-mice/