The Role Of α-synuclein Transmission In The Peripheral Nervous System In The Pathological Process Of Parkinson’s Disease

Parkinson’s disease is the second most common neurodegenerative disease around the world,and the incidence is as high as 1.7% among people over 65 years old.The presence of a large number of Lewy bodies in neurons has received extensive attention in the study of Parkinson’s pathological development.Whether phosphorylated α-synuclein,the main component of these Lewy bodies,originated in the peripheral nervous system or the central nervous system is still a matter of debate.Some studies indicated that pathologic α-synuclein in Parkinson’s disease may be caused by some pathogenic factors and then pass through the intestinal mucosa,and then enter the central nervous system from the peripheral nervous system via the vector of the vagus nerve fibers,which leading to central nervous system lesions.In this study,we investigated the pathologic transmission of α-synuclein from the peripheral nervous system to the central nervous system by injecting different forms of α-synuclein into the gastrointestinal tract.Our results show that α-synuclein preform fiber(PFF)induced insoluble protein aggregates in the gastrointestinal neurons of mice and macaques.We then observed α-synuclein aggregates in the vagus nerve to the central nervous system of mice four weeks after injection of PFF,suggesting that the α-synuclein might transmitted from the intestine to the brain via the vagus nerve.We also observed α-synuclein aggregates in the dorsal motor nucleus of the macaque four months after injection,it is the first time to show that enteric injection of α-synuclein induced pathologic α-synuclein in the dorsal nucleus of the vagus nerve in non-human primates.Furthermore,our results in mice also suggest that endogenous α-synuclein was involved in the transmission of synucleinopathy and inflammation played a role in neurodegeneration.