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KIT-13,一种新型缩醛磷脂衍生物,可减轻神经炎症并增强认知能力。

KIT-13, a novel plasmalogen derivative, attenuates neuroinflammation and amplifies cognition.

作者信息

Hossain Md Shamim, Mawatari Shiro, Honsho Masanori, Okauchi Tatsuo, Fujino Takehiko

机构信息

Division of Lipid Cell Biology, Institute of Rheological Functions of Food, Fukuoka, Japan.

Department of Neuroinflammation and Brain Fatigue Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

出版信息

Front Cell Dev Biol. 2024 Sep 2;12:1443536. doi: 10.3389/fcell.2024.1443536. eCollection 2024.

Abstract

Plasmalogens (Pls) are specialized phospholipids integral to brain health, whose decline due to aging and stress contributes to cognitive impairment and neuroinflammation. This study explores the potential of a novel Pls derivative, KIT-13 (1-O-octadecyl-2-arachidonoyl-sn-glycerol-3-phosphoethanolamine), in mitigating neuroinflammation and enhancing cognition. When administered to mice, KIT-13 exhibited potent memory enhancement attributed to upregulated brain-derived neurotrophic factor (BDNF), a key player in cognitive processes. experiments with neuronal cells revealed KIT-13's ability to induce robust cellular signaling, surpassing natural plasmalogens. KIT-13 also promoted neurogenesis and inhibited apoptosis of neuronal-like cells, highlighting its potential in fostering neuronal growth and plasticity. Additionally, KIT-13 treatments reduced pro-inflammatory cytokine expression and attenuated glial activation in the brain. KIT-13's superior efficacy over natural Pls positions it as a promising therapeutic candidate for neurodegenerative conditions such as Alzheimer's disease, characterized by cognitive decline and neuroinflammation. This study presents KIT-13 as an innovative approach for addressing cognitive impairment and neuroinflammatory pathologies.

摘要

缩醛磷脂(Pls)是对大脑健康至关重要的特殊磷脂,其因衰老和应激而减少会导致认知障碍和神经炎症。本研究探索了一种新型缩醛磷脂衍生物KIT-13(1-O-十八烷基-2-花生四烯酰基-sn-甘油-3-磷酸乙醇胺)在减轻神经炎症和增强认知方面的潜力。给小鼠施用KIT-13后,其表现出强大的记忆增强作用,这归因于脑源性神经营养因子(BDNF)的上调,BDNF是认知过程中的关键因子。对神经元细胞进行的实验表明,KIT-13能够诱导强大的细胞信号传导,超过天然缩醛磷脂。KIT-13还促进神经发生并抑制类神经元细胞的凋亡,突出了其在促进神经元生长和可塑性方面的潜力。此外,KIT-13处理降低了大脑中促炎细胞因子的表达并减弱了胶质细胞的激活。KIT-13相对于天然缩醛磷脂具有更高的疗效,使其成为治疗以认知衰退和神经炎症为特征的神经退行性疾病(如阿尔茨海默病)的有前景的候选药物。本研究将KIT-13作为解决认知障碍和神经炎症性病理的创新方法进行了介绍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0776/11402709/9b2d0a53326a/fcell-12-1443536-g001.jpg

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