RESEARCH PAPER
Neuroprotective effects of serum- and glucocorticoid-regulated kinase 1 protein in a Parkinson's disease model.
Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disorder associated with non-motor symptoms including autonomic dysfunction, cognitive decline, depression, and gastrointestinal dysfunction. PD is characterized by reductions in the number of dopaminergic neurons and the tyrosine hydroxylase (TH) enzyme level; however, the reasons for these reductions have not been elucidated. The accumulation of α-syneclein (α-syn) is the neuropathological characteristic of PD. In this study, we investigated whether serum- and glucocorticoid-regulated kinase 1 (SGK1) treatment may have a positive effect on neurodegenerative changes in PD. SGK1, a serine/threonine-protein kinase involved in Na+/K+ pump activity, is encoded by sgk1. SGK1-myc, transiently expressed in tobacco leaves, was extracted and used to treat SW480 and SH-SY5Y cells. The changes in the expression levels of the factors related to PD, i.e., TH and α-syn, were investigated in the cells and in the colons of the 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine-induced PD model. The SGK1 expression level was associated with TH and α-syn expression levels, and SGK1 treatment positively affected PD-related pathological symptoms. In addition, SGK1 treatment led to improved TH expression in the substantia nigra and striatum regions. The increase in SGK1 expression following treatment with the recombinant SGK1-myc protein resulted in beneficial alterations in the pathological factors associated with PD. These findings position SGK1 as a potential therapeutic target for early-stage PD therapy, as it is associated with the Na+/K+ pump and gastrointestinal dysfunction, features often disrupted in early PD.