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.

缩醛磷脂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 位上含有乙烯基醚连接的烷基链，并且通常在 sn-2 位上含有多不饱和脂肪酰基链。缩醛磷脂对人类健康至关重要，在神经元发育、免疫反应和作为内源性抗氧化剂中发挥着重要作用。然而，缩醛磷脂的这些和其他生物学功能的机制基础尚未明确。脂质组学研究表明，在许多疾病状态下，包括神经退行性疾病和心脏代谢疾病，缩醛磷脂水平降低，凸显了缩醛磷脂调节作为治疗策略的潜力。

已经提出了多种方法来上调不同临床环境中缩醛磷脂的水平；这些包括使用肌醇或称为烷基甘油的天然代谢前体进行饮食干预。缩醛磷脂调节已用于临床前和临床研究，以预防神经退行性疾病、动脉粥样硬化、胰岛素抵抗和肝脂肪变性的发生和/或减轻其进展。这些研究为缩醛磷脂在疾病中的机制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策略以及治疗应用的最新进展，重点关注神经退行性和心脏代谢疾病。