神经炎症
小胶质细胞
核黄素
炎症
化学
细胞生物学
神经科学
生物
生物化学
免疫学
作者
Mengran Zhang,Huaqing Chen,Wenlong Zhang,Yan Liu,Liuyan Ding,Junhua Gong,Runfang Ma,Shaohui Zheng,Yunlong Zhang
标识
DOI:10.1002/advs.202300180
摘要
Abstract Neuroinflammation, for which microglia are the predominant contributors, is a significant risk factor for cognitive dysfunction. Riboflavin (also known as vitamin B2) ameliorates cognitive impairment via anti‐oxidative stress and anti‐inflammation properties; however, the underlying mechanisms linking riboflavin metabolism and microglial function in cognitive impairment remain unclear. Here, it is demonstrated that riboflavin kinase (RFK), a critical enzyme in riboflavin metabolism, is specifically expressed in microglia. An intermediate product of riboflavin, flavin mononucleotide (FMN), inhibited RFK expression via regulation of lysine‐specific methyltransferase 2B (KMT2B). FMN supplementation attenuated the pro‐inflammatory TNFR1/NF‐ κ B signaling pathway, and this effect is abolished by KMT2B overexpression. To improve the limited anti‐inflammatory efficiency of free FMN, a biomimetic microglial nanoparticle strategy (designated as MNPs@FMN) is established, which penetrated the blood brain barrier with enhanced microglial‐targeted delivery efficiency. Notably, MNPs@FMN ameliorated cognitive impairment and dysfunctional synaptic plasticity in a lipopolysaccharide‐induced inflammatory mouse model and in a 5xFAD mouse model of Alzheimer's disease. Taken together, biomimetic microglial delivery of FMN may serve as a potential therapeutic approach for inflammation‐dependent cognitive decline.
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