Gpr35 Expression Mitigates Neuroinflammation and Enriches Gut Lactobacillus to Relieve Parkinson's Disease.

IF 10.7 1区 综合性期刊 Q1 Multidisciplinary
Research Pub Date : 2025-08-25 eCollection Date: 2025-01-01 DOI:10.34133/research.0846
Tianyu Meng, Yufei Zhang, Shoupeng Fu, Shaohua Ma
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引用次数: 0

Abstract

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.

Gpr35表达减轻神经炎症和丰富肠道乳酸菌缓解帕金森病
帕金森病(PD)与肠-脑轴和肠道微生物群改变有关,但其功能机制仍有待阐明。在这项研究中,我们发现G蛋白偶联受体35 (Gpr35)是PD背景下肠脑关联的关键调节因子。在1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的PD模型中,采用Gpr35基因敲除(Gpr35-/-)和野生型(WT)小鼠,研究Gpr35基因敲除(Gpr35-/-)对运动功能、神经炎症和多巴胺能神经变性的影响;在小胶质细胞和多巴胺能细胞模型中,采用Gpr35激动剂犬尿酸(KYNA)和小干扰RNA,研究Gpr35基因上调/下调对神经炎症、氧化应激和神经元凋亡的影响。证实Gpr35可能通过调节神经炎症和肠道微生物群及代谢物组成,特别是通过丰富乳酸杆菌,实质性调节酪氨酸代谢、神经活性配体-受体相互作用和色氨酸代谢途径,从而抑制PD的进展,从而预防PD。我们的研究结果强调了靶向Gpr35影响肠道微生物群和中枢神经系统的潜力,为PD的治疗提供了新的见解。
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来源期刊
Research
Research Multidisciplinary-Multidisciplinary
CiteScore
13.40
自引率
3.60%
发文量
0
审稿时长
14 weeks
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.
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