Work

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

Year: 2025

Type: article

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.

Source: Research

DOI: 10.34133/research.0846

Authors: Tianyu Meng, Yufei Zhang, Shoupeng Fu, Shaohua Ma

Institutions: Tsinghua Shenzhen International Graduate School, Tsinghua University, Jilin University

Language: English

Topic: Parkinson's Disease Mechanisms and Treatments

Subfield: Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,500