A growing body of evidence indicates an association between flavin-containing monooxygenase (FMO) and neurodegeneration, including Parkinson’s disease (PD); however, the details of this association are unclear. We previously showed that the level of Fmo1 mRNA is decreased in an in vitro rotenone model of parkinsonism. To further explore the potential involvement of FMO1 deficiency in parkinsonism, we generated Fmo1 knockout (KO) mice and examined the survival of dopaminergic neurons and relative changes. Fmo1 KO mice exhibited loss of tyrosine hydroxylase-positive neurons, decreased levels of tyrosine hydroxylase and Parkin proteins, and increased levels of pro-inflammatory cytokines (IL1β and IL6) in the nigrostriatal region. Moreover, the protein levels of PTEN induced kinase 1 (PINK1) and p62, and the Microtubule associated protein 1 light chain 3 (LC3)-II/I ratio were not significantly altered in Fmo1 KO mice (P > 0.05). FMO1 deficiency promotes neuroinflammation in dopaminergic neurons in mice, thus may plays a potential pathological role in dopaminergic neuronal loss. These findings may provide new insight into the pathogenesis of PD.

越来越多的证据表明含黄素的单加氧酶 (FMO) 与包括帕金森病 (PD) 在内的神经退行性变之间存在关联；然而，这种关联的细节尚不清楚。我们之前表明，在帕金森症的体外鱼藤酮模型中， Fmo1 mRNA 的水平降低。为了进一步探索 FMO1 缺乏症与帕金森病的潜在关系，我们生成了 FMO1敲除 (KO) 小鼠并检查了多巴胺能神经元的存活率和相关变化。Fmo1KO 小鼠表现出酪氨酸羟化酶阳性神经元丢失，酪氨酸羟化酶和帕金蛋白水平降低，黑质纹状体区域促炎细胞因子（IL1β 和 IL6）水平升高。此外， Fmo1 KO小鼠PTEN诱导激酶1（PINK1）和p62蛋白水平及微管相关蛋白1轻链3（LC3）-II/I比值无明显变化（ P  > 0.05）。FMO1缺乏促进小鼠多巴胺能神经元的神经炎症，因此可能在多巴胺能神经元丢失中发挥潜在的病理作用。这些发现可能为 PD 的发病机制提供新的见解。