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Plasmalogens: A potential therapeutic target for neurodegenerative and cardiometabolic disease
Progress in Lipid Research ( IF 14.0 ) Pub Date : 2019-04-08 , DOI: 10.1016/j.plipres.2019.04.003
Sudip Paul , Graeme I. Lancaster , Peter J. Meikle

Plasmalogens are a class of membrane glycerophospholipids with unique properties. They contain a vinyl-ether linked alkyl chain at the sn-1 position of the glycerol backbone and, typically, a polyunsaturated fatty acyl chain at the sn-2 position. Plasmalogens are critical for human health and have established roles in neuronal development, the immune response and as endogenous antioxidants. However, the mechanistic bases of these and other biological functions of plasmalogens are not well defined. Lipidomic studies have characterised reduced levels of plasmalogens in a number of disease states, including neurodegenerative and cardiometabolic disease, highlighting the potential of plasmalogen modulation as a therapeutic strategy.

A number of approaches have been proposed to upregulate plasmalogen levels in different clinical settings; these include dietary intervention with inositol or the naturally occurring metabolic precursors known as alkylglycerols. Plasmalogen modulation has been utilised in both preclinical and clinical studies to prevent onset and/or attenuate progression of neurodegenerative diseases, atherosclerosis, insulin resistance and hepatosteatosis. These studies are providing new insight into the mechanistic role of plasmalogens in disease and their therapeutic potential.

In this review, we will examine the strategies for plasmalogen modulation and recent progress toward therapeutic applications with a focus on neurodegenerative and cardiometabolic disease.



中文翻译:

纤溶酶原:神经退行性疾病和心脏代谢疾病的潜在治疗靶标

纤溶酶原是一类具有独特性质的膜甘油磷脂。它们在甘油主链的sn-1位置包含一个乙烯基醚连接的烷基链,通常在sn-2位置包含一个多不饱和脂肪酰基链。纤溶酶原对人类健康至关重要,并且在神经元发育,免疫反应和作为内源性抗氧化剂方面已经确立了作用。然而,缩醛磷脂的这些和其他生物学功能的机制基础还没有很好的定义。脂质组学研究的特征是在许多疾病状态(包括神经退行性疾病和心脏代谢疾病)中缩醛磷脂水平降低,突出了缩醛磷脂调节作为治疗策略的潜力。

已经提出了许多在不同临床环境中上调缩醛磷脂水平的方法。其中包括肌醇或称为烷基甘油的天然代谢前体的饮食干预。在临床前和临床研究中均已使用了血浆生成原调节剂,以预防和/或减轻神经退行性疾病,动脉粥样硬化,胰岛素抵抗和肝脂肪变性的进展。这些研究为缩醛磷脂在疾病中的作用及其治疗潜力提供了新的见解。

在这篇综述中,我们将研究缩醛磷脂调节的策略以及在神经退行性疾病和心脏代谢性疾病方面的治疗应用的最新进展。

更新日期:2019-04-08
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