Rebamipide (Mucosta®), a clinically approved drug, alleviates neuroinflammation and dopaminergic neurodegeneration in a Parkinson’s disease model

作者：Hye‐Sun Lim, Jin‐Young Park, Eunjeong Kim, Wonhwa Lee, Hwi‐yeol Yun, Seung Hoon Lee, Gunhyuk Park · 发表于：Journal of Neuroinflammation · 年份：2025 · DOI：10.1186/s12974-025-03461-z · 被引用次数：11 · 研究领域：Parkinson's Disease Mechanisms and Treatments、Pharmacological Receptor Mechanisms and Effects、Tryptophan and brain disorders

Parkinson’s disease (PD) is characterized by dopaminergic neuron loss, neuroinflammation, and motor dysfunction. PD is a multifactorial disease, with neuroinflammation driven by NLRP3 inflammasome activation representing an important component of its pathological progression. Therefore, we aimed to evaluate the therapeutic potential of rebamipide (Mucosta®), a clinically approved anti-inflammatory agent, in PD by targeting the NLRP3 inflammasome. Specifically, we examined the effects of rebamipide on neuroinflammation, dopaminergic neuron preservation, and motor deficits using BV2 microglia cells and a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced mouse model. Rebamipide alleviated microglial activation and downstream neuroinflammation by suppressing the NLRP3–NEK7 interaction, resulting in dopaminergic neuron protection in the MPTP-induced PD model. Rebamipide downregulated IL-1β levels in BV2 microglia cells treated with α-synuclein and MPP+. Molecular docking analysis revealed a high binding affinity between rebamipide and the NLRP3-NEK7 interaction interface. Surface plasmon resonance analysis confirmed the direct binding of rebamipide to NLRP3, with notable kinetic affinity, supporting its role as a novel NLRP3 inflammasome inhibitor. Rebamipide significantly downregulated IL-1β levels, microglial activation, and dopaminergic neuron loss in the MPTP mouse model by disrupting inflammasome activation. Rebamipide preserved dopamine levels in the striatum an...