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Exendin-4 and linagliptin attenuate neuroinflammation in a mouse model of Parkinson's disease

Neural Regeneration Research 2023年第8期18卷 1818-1826页

作者： Hai-Yang Yu Tong Sun Zhen Wang Hong Li Duo Xu Jing An Lu-Lu Wen Jia-Yi Li Wen Li Juan Feng Department of Neurology Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina Department of Pediatrics Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina Laboratory of Research in Parkinson’s Disease and Related Disorders Health Sciences InstituteChina Medical UniversityShenyangLiaoning ProvinceChina Neural Plasticity and Repair Unit Department of Experimental Medical ScienceLund UniversityLundSweden

Use of glucagon-like peptide-1 receptor agonist or dipeptidyl peptidase 4 inhibitor has been shown to lower the incidence of Parkinson's disease in patients with diabetes ***,using these two treatments may help treat Parkinson's *** further investigate the mechanisms of action of these two compounds,we established a model of Parkinson's disease by treating mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and then subcutaneously injected them with the glucagon-like peptide-1 receptor agonist exendin-4 or the dipeptidyl peptidase 4 inhibitor *** found that both exendin-4 and linagliptin reversed motor dysfunction,glial activation,and dopaminergic neuronal death in this *** addition,both exendin-4 and linagliptin induced microglial polarization to the anti-inflammatory M2 phenotype and reduced pro-inflammatory cytokine ***,in vitro experiments showed that treatment with exendin-4 and linagliptin inhibited activation of the nucleotide-binding oligomerization domain-and leucine-rich-repeat-and pyrin-domaincontaining 3/caspase-1/interleukin-1βpathway and subsequent pyroptosis by decreasing the production of reactive oxygen *** findings suggest that exendin-4 and linagliptin exert neuroprotective effects by attenuating neuroinflammation through regulation of microglial polarization and the nucleotidebinding oligomerization domain-and leucine-rich-repeat-and pyrin-domain-containing 3/caspase-1/interleukin-1βpathway in a mouse model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,***,these two drugs may serve as novel anti-inflammatory treatments for Parkinson's disease.

关键词： diabetes mellitus dipeptidyl peptidase 4 inhibitor exendin-4 glucagon-like peptide-1 receptor agonist 1-methyl-4-phenyl-1 2 3 6-tetrahydropyridine linagliptin microglia neuroinflammation NLRP3 inflammasome Parkinson's disease pyroptosis

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