Association between Decreased SGK1 and Increased Intestinal -Synuclein in an MPTP Mouse Model of Parkinson's Disease

Parkinson's disease (PD) is a globally common progressive neurodegenerative disease resulting from the loss of dopaminergic neurons in the brain. Increased alpha-synuclein (alpha-syn) is associated with the degeneration of dopaminergic neurons and non-motor symptoms like gastrointestinal disorders. In this study, we investigated the association between serum/glucocorticoid-related kinase 1 (SGK1) and alpha-syn in the colon of a PD mouse model. SGK1 and alpha-syn expression patterns were opposite in the surrounding colon tissue, with decreased SGK1 expression and increased alpha-syn expression in the PD group. Immunofluorescence analyses revealed the colocation of SGK1 and alpha-syn; the PD group demonstrated weaker SGK1 expression and stronger alpha-syn expression than the control group. Immunoblotting analysis showed that Na+/K+ pump ATPase alpha 1 expression levels were significantly increased in the PD group. In SW480 cells with SGK1 knockdown using SGK1 siRNA, decreasing SGK1 levels corresponded with significant increases in the expression levels of alpha-syn and ATPase alpha 1. These results suggest that SGK1 significantly regulates Na+/K+ pump ATPase, influencing the relationship between electrolyte balance and fecal formation in the PD mouse model. Gastrointestinal disorders are some of the major prodromal symptoms of PD. Therefore, modulating SGK1 expression could be an important strategy for controlling PD.