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

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 

机构地区：[1]Department of Neurology,Shengjing Hospital of China Medical University,Shenyang,Liaoning Province,China [2]Department of Pediatrics,Shengjing Hospital of China Medical University,Shenyang,Liaoning Province,China [3]Laboratory of Research in Parkinson’s Disease and Related Disorders,Health Sciences Institute,China Medical University,Shenyang,Liaoning Province,China [4]Neural Plasticity and Repair Unit,Department of Experimental Medical Science,Lund University,Lund,Sweden

出　　处：《Neural Regeneration Research》2023年第8期1818-1826,共9页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,Nos.81771271(to JF),31800898(to WL),81430025(to JYL),and U1801681(to JYL);Key Research and Development Program of Liaoning Province,No.2020JH2/10300047(to JF);the Key Field Research Development Program of Guangdong Province,No.2018B030337001(to JYL);the Outstanding Scientific Fund of Shengjing Hospital,No.M0475(to JF)。

摘　　要：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 mellitus.Therefore,using these two treatments may help treat Parkinson's disease.To 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 linagliptin.We found that both exendin-4 and linagliptin reversed motor dysfunction,glial activation,and dopaminergic neuronal death in this model.In addition,both exendin-4 and linagliptin induced microglial polarization to the anti-inflammatory M2 phenotype and reduced pro-inflammatory cytokine secretion.Moreover,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 species.These 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-1,2,3,6-tetrahydropyridine.Therefore,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 

分 类 号：R742.5[医药卫生—神经病学与精神病学]