Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi, PR China.
J Neurochem. 2019 Aug;150(4):441-452. doi: 10.1111/jnc.14694. Epub 2019 Apr 1.
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 < 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 < 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.
虽然胰高血糖素样肽-1 (GLP-1) 被报道对帕金森病有积极影响,但它的半衰期极短,极大地阻碍了其临床应用。在这项研究中,构建了持续表达 GLP-1 的 MG1363-pMG36e-GLP-1 品系,以治疗 MPTP 诱导的帕金森病模型中的帕金森病。在我们的研究中,口服补充 MG1363-pMG36e-GLP-1 显著(p < 0.05)减轻了 MPTP 诱导的运动障碍,增加了酪氨酸羟化酶阳性神经元,抑制了小胶质细胞和星形胶质细胞的激活,并下调了几种炎症相关分子的表达。此外,MG1363-pMG36e-GLP-1 显著(p < 0.01)减少了肠道病原体肠杆菌科的数量,显著增加了益生菌乳杆菌和阿克曼氏菌的数量。这些数据表明,MG1363-pMG36e-GLP-1 可能是一种治疗帕金森病的新方法。