{"title":"Gpr35表达减轻神经炎症和丰富肠道乳酸菌缓解帕金森病","authors":"Tianyu Meng, Yufei Zhang, Shoupeng Fu, Shaohua Ma","doi":"10.34133/research.0846","DOIUrl":null,"url":null,"abstract":"<p><p>Parkinson's disease (PD) is associated with gut-brain axis and gut microbiota alterations, but the functioning mechanism remains to be elucidated. In this study, we identified G protein-coupled receptor 35 (Gpr35) as a key regulator for the gut-brain association under the PD context. It investigated the impact of Gpr35 deficiency on motor function, neuroinflammation, and dopaminergic neurodegeneration, using the Gpr35 knockout (Gpr35<sup>-/-</sup>) and wild-type (WT) mice in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model, and Gpr35 up-/down-regulation on reverse neuroinflammation, oxidative stress, and neuronal apoptosis using Gpr35 agonist kynurenic acid (KYNA) and small interfering RNA in microglial and dopaminergic cell models. It was confirmed that Gpr35 may prevent PD by modulating neuroinflammation and gut microbiota and metabolite composition, specifically through enriching <i>Lactobacillus</i>, and substantially regulating tyrosine metabolism, neuroactive ligand-receptor interaction, and tryptophan metabolism pathways, thereby inhibiting the progression of PD. Our findings highlight the potential of targeting Gpr35 to influence both the gut microbiota and central nervous system, offering new insights into the treatment of PD.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0846"},"PeriodicalIF":10.7000,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376290/pdf/","citationCount":"0","resultStr":"{\"title\":\"Gpr35 Expression Mitigates Neuroinflammation and Enriches Gut <i>Lactobacillus</i> to Relieve Parkinson's Disease.\",\"authors\":\"Tianyu Meng, Yufei Zhang, Shoupeng Fu, Shaohua Ma\",\"doi\":\"10.34133/research.0846\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Parkinson's disease (PD) is associated with gut-brain axis and gut microbiota alterations, but the functioning mechanism remains to be elucidated. In this study, we identified G protein-coupled receptor 35 (Gpr35) as a key regulator for the gut-brain association under the PD context. It investigated the impact of Gpr35 deficiency on motor function, neuroinflammation, and dopaminergic neurodegeneration, using the Gpr35 knockout (Gpr35<sup>-/-</sup>) and wild-type (WT) mice in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model, and Gpr35 up-/down-regulation on reverse neuroinflammation, oxidative stress, and neuronal apoptosis using Gpr35 agonist kynurenic acid (KYNA) and small interfering RNA in microglial and dopaminergic cell models. It was confirmed that Gpr35 may prevent PD by modulating neuroinflammation and gut microbiota and metabolite composition, specifically through enriching <i>Lactobacillus</i>, and substantially regulating tyrosine metabolism, neuroactive ligand-receptor interaction, and tryptophan metabolism pathways, thereby inhibiting the progression of PD. Our findings highlight the potential of targeting Gpr35 to influence both the gut microbiota and central nervous system, offering new insights into the treatment of PD.</p>\",\"PeriodicalId\":21120,\"journal\":{\"name\":\"Research\",\"volume\":\"8 \",\"pages\":\"0846\"},\"PeriodicalIF\":10.7000,\"publicationDate\":\"2025-08-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12376290/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Research\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.34133/research.0846\",\"RegionNum\":1,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"Multidisciplinary\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Research","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.34133/research.0846","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"Multidisciplinary","Score":null,"Total":0}
Gpr35 Expression Mitigates Neuroinflammation and Enriches Gut Lactobacillus to Relieve Parkinson's Disease.
Parkinson's disease (PD) is associated with gut-brain axis and gut microbiota alterations, but the functioning mechanism remains to be elucidated. In this study, we identified G protein-coupled receptor 35 (Gpr35) as a key regulator for the gut-brain association under the PD context. It investigated the impact of Gpr35 deficiency on motor function, neuroinflammation, and dopaminergic neurodegeneration, using the Gpr35 knockout (Gpr35-/-) and wild-type (WT) mice in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model, and Gpr35 up-/down-regulation on reverse neuroinflammation, oxidative stress, and neuronal apoptosis using Gpr35 agonist kynurenic acid (KYNA) and small interfering RNA in microglial and dopaminergic cell models. It was confirmed that Gpr35 may prevent PD by modulating neuroinflammation and gut microbiota and metabolite composition, specifically through enriching Lactobacillus, and substantially regulating tyrosine metabolism, neuroactive ligand-receptor interaction, and tryptophan metabolism pathways, thereby inhibiting the progression of PD. Our findings highlight the potential of targeting Gpr35 to influence both the gut microbiota and central nervous system, offering new insights into the treatment of PD.
期刊介绍:
Research serves as a global platform for academic exchange, collaboration, and technological advancements. This journal welcomes high-quality research contributions from any domain, with open arms to authors from around the globe.
Comprising fundamental research in the life and physical sciences, Research also highlights significant findings and issues in engineering and applied science. The journal proudly features original research articles, reviews, perspectives, and editorials, fostering a diverse and dynamic scholarly environment.