Abstract
Patients with Parkinson's disease (PD) have gastrointestinal motility disorders, which are common non-motor symptoms. However, the reasons for these motility disorders remain unclear. Increased alpha-synuclein (α-syn) is considered an important factor in peristalsis dysfunction in colonic smooth muscles in patients with PD. In this study, the morphological changes and association between serping1 and α-syn were investigated in the colon of the 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-induced chronic PD model. Increased serping1 and α-syn were noted in the colon of the PD model, and decreased serping1 also induced a decrease in α-syn in C2C12 cells. Serping1 is a major regulator of physiological processes in the kallikrein-kinin system, controlling processes including inflammation and vasodilation. The kinin system also comprises bradykinin and bradykinin receptor 1. The factors related to the kallikrein-kinin system, bradykinin, and bradykinin receptor 1 were regulated by serping1 in C2C12 cells. The expression levels of bradykinin and bradykinin receptor 1, modulated by serping1 also increased in the colon of the PD model. These results suggest that the regulation of increased serping1 could alleviate Lewy-type α-synucleinopathy, a characteristic of PD. Furthermore, this study could have a positive effect on the early stages of PD progression because of the perception that α-syn in colonic tissues is present prior to the development of PD motor symptoms.