Tremblay Marie-Ève, Almsherqi Zakaria A, Deng Yuru
Division of Medical Sciences, University of Victoria, Victoria, British Columbia, Canada.
Axe Neurosciences, Centre de recherche du CHU de Québec-Université Laval, Québec City, Canada.
Biofactors. 2022 Nov;48(6):1203-1216. doi: 10.1002/biof.1916. Epub 2022 Nov 12.
Fatty acids and phospholipid molecules are essential for determining the structure and function of cell membranes, and they hence participate in many biological processes. Platelet activating factor (PAF) and its precursor plasmalogen, which represent two subclasses of ether phospholipids, have attracted increasing research attention recently due to their association with multiple chronic inflammatory, neurodegenerative, and metabolic disorders. These pathophysiological conditions commonly involve inflammatory processes linked to an excess presence of PAF and/or decreased levels of plasmalogens. However, the molecular mechanisms underlying the roles of plasmalogens in inflammation have remained largely elusive. While anti-inflammatory responses most likely involve the plasmalogen signal pathway; pro-inflammatory responses recruit arachidonic acid, a precursor of pro-inflammatory lipid mediators which is released from membrane phospholipids, notably derived from the hydrolysis of plasmalogens. Plasmalogens per se are vital membrane phospholipids in humans. Changes in their homeostatic levels may alter cell membrane properties, thus affecting key signaling pathways that mediate inflammatory cascades and immune responses. The plasmalogen analogs of PAF are also potentially important, considering that anti-PAF activity has strong anti-inflammatory effects. Plasmalogen replacement therapy was further identified as a promising anti-inflammatory strategy allowing for the relief of pathological hallmarks in patients affected by chronic diseases with an inflammatory component. The aim of this Short Review is to highlight the emerging roles and implications of plasmalogens in chronic inflammatory disorders, along with the promising outcomes of plasmalogen replacement therapy for the treatment of various PAF-related chronic inflammatory pathologies.
脂肪酸和磷脂分子对于确定细胞膜的结构和功能至关重要，因此它们参与许多生物过程。血小板活化因子（PAF）及其前体缩醛磷脂，代表醚磷脂的两个亚类，由于它们与多种慢性炎症、神经退行性和代谢紊乱相关，最近引起了越来越多的研究关注。这些病理生理状况通常涉及与PAF过量存在和/或缩醛磷脂水平降低相关的炎症过程。然而，缩醛磷脂在炎症中作用的分子机制在很大程度上仍然难以捉摸。虽然抗炎反应很可能涉及缩醛磷脂信号通路；促炎反应会募集花生四烯酸，这是一种促炎脂质介质的前体，从膜磷脂中释放出来，特别是来自缩醛磷脂的水解。缩醛磷脂本身是人类重要的膜磷脂。它们稳态水平的变化可能会改变细胞膜特性，从而影响介导炎症级联反应和免疫反应的关键信号通路。考虑到抗PAF活性具有强大的抗炎作用，PAF的缩醛磷脂类似物也可能很重要。缩醛磷脂替代疗法进一步被确定为一种有前景的抗炎策略，可缓解患有炎症成分的慢性疾病患者的病理特征。本短篇综述的目的是强调缩醛磷脂在慢性炎症性疾病中的新作用和影响，以及缩醛磷脂替代疗法治疗各种与PAF相关的慢性炎症性疾病的前景。
