Neuroprotective effects of an engineered commensal bacterium in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine Parkinson disease mouse model via producing glucagon-like peptide-1.

Abstract

While glucagon-like peptide-1 (GLP-1) was reported to have a positive impact on Parkinson disease, it is extremely short half-life greatly hindered its clinical use. In this study, the mouse strain MG1363-pMG36e-GLP-1 was engineered to continuously express GLP-1 to treat Parkinson disease in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated Parkinson disease model. In our study, oral supplementation with MG1363-pMG36e-GLP-1 significantly (p&#xa0;<&#xa0;0.05) reduced MPTP-induced locomotor impairments, increased tyrosine hydroxylase-positive neurons, suppressed microglia and astrocyte activation, and down-regulated expression of several inflammation-related molecules. In addition, MG1363-pMG36e-GLP-1 significantly (p&#xa0;<&#xa0;0.01) reduced intestinal pathogen Enterobacteriaceae and markedly enhanced the number of probiotic Lactobacillus and Akkermansia. These data suggest that MG1363-pMG36e-GLP-1 could be a novel therapeutic means for Parkinson disease.