The engineered probiotic strain Lactococcus lactis MG1363-pMG36e-GLP-1 regulates microglial polarization and gut dysbiosis in a transgenic mouse model of Parkinson's disease
Mengyun Yue1
Tingtao Chen2
Wenjie Chen3
Jing Wei2
Bin Liao1
Jie Zhang1
Fangjun Li1
Daojun Hong1
Xin Fang1
1.Department of Neurology,The First Affiliated Hospital,Jiangxi Medical College,Nanchang University,Nanchang,Jiangxi Province,China2.National Engineering Research Center of Bioengineering Drugs and Technologies,Institute of Translational Medicine,Nanchang University,Nanchang,Jiangxi Province,China3.National Engineering Research Center of Bioengineering Drugs and Technologies,Institute of Translational Medicine,Nanchang University,Nanchang,Jiangxi Province,China;Queen Mary School,Jiangxi Medical College,Nanchang University,Nanchang,Jiangxi Province,China
摘要：Parkinson's disease is characterized by synucleinopathy-associated neurodegeneration.Previous studies have shown that glucagon-like peptide-1(GLP-1)has beneficial effects in a mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.However,the effect of GLP-1 on intrinsic synuclein malfunction remains unclear.In this study,we investigated the effect of Lactococcus lactis MG1363-pMG36e-GLP-1 on parkinsonism in SncaA53T transgenic mice and explored the underlying mechanisms.Our data showed that Lactococcus lactis MG1363-pMG36e-GLP-1 inhibited dopaminergic neuronal death,reduced pathological aggregation of α-synuclein,and decreased movement disorders in SncaA53T transgenic mice.Furthermore,Lactococcus lactis MG1363-pMG36e-GLP-1 downregulated lipopolysaccharide-related inflammation,reduced cerebral activation of microglia and astrocytes,and promoted cell survival via the GLP-1 receptor/PI3K/Akt pathway in the substantia nigra.Additionally,Lactococcus lactis MG1363-pMG36e-GLP-1 decreased serum levels of pro-inflammatory molecules including lipopolysaccharide,lipopolysaccharide binding protein,interleukin-1β,and interleukin-6.Gut histopathology and western blotting further revealed that Lactococcus lactis MG1363-pMG36e-GLP-1 increased the expression of gut integrity-related proteins and reduced lipopolysaccharide-related inflammation by reversing gut dysbiosis in SncaA53T transgenic mice.Our findings showed that the beneficial effect of Lactococcus lactis MG1363-pMG36e-GLP-1 on parkinsonism traits in SncaA53T transgenic mice is mediated by microglial polarization and the reversal of dysbiosis.Collectively,our findings suggest that Lactococcus lactis MG1363-pMG36e-GLP-1 is a promising therapeutic agent for the treatment of Parkinson's disease.
机标关键词：transgenicparkinsonstrainmousemodeldiseasedysbiosisengineered
论文发表日期：2026-03-30
在线出版日期：2026-03-18（本平台首次上网日期，不代表文献的发表时间）
页数：11( 1211-1221 )
英文信息