Bozelli José Carlos, Azher Sayed, Epand Richard M
Department of Biochemistry and Biomedical Sciences, Health Sciences Centre, McMaster University, Hamilton, ON, Canada.
Front Physiol. 2021 Oct 21;12:730829. doi: 10.3389/fphys.2021.730829. eCollection 2021.
It is becoming widely acknowledged that lipids play key roles in cellular function, regulating a variety of biological processes. Lately, a subclass of glycerophospholipids, namely plasmalogens, has received increased attention due to their association with several degenerative and metabolic disorders as well as aging. All these pathophysiological conditions involve chronic inflammatory processes, which have been linked with decreased levels of plasmalogens. Currently, there is a lack of full understanding of the molecular mechanisms governing the association of plasmalogens with inflammation. However, it has been shown that in inflammatory processes, plasmalogens could trigger either an anti- or pro-inflammation response. While the anti-inflammatory response seems to be linked to the entire plasmalogen molecule, its pro-inflammatory response seems to be associated with plasmalogen hydrolysis, ., the release of arachidonic acid, which, in turn, serves as a precursor to produce pro-inflammatory lipid mediators. Moreover, as plasmalogens comprise a large fraction of the total lipids in humans, changes in their levels have been shown to change membrane properties and, therefore, signaling pathways involved in the inflammatory cascade. Restoring plasmalogen levels by use of plasmalogen replacement therapy has been shown to be a successful anti-inflammatory strategy as well as ameliorating several pathological hallmarks of these diseases. The purpose of this review is to highlight the emerging role of plasmalogens in chronic inflammatory disorders as well as the promising role of plasmalogen replacement therapy in the treatment of these pathologies.
脂质在细胞功能中发挥关键作用,调节多种生物过程,这一点正得到广泛认可。最近,甘油磷脂的一个亚类,即缩醛磷脂,因其与多种退行性和代谢性疾病以及衰老有关而受到越来越多的关注。所有这些病理生理状况都涉及慢性炎症过程,而这与缩醛磷脂水平降低有关。目前,对于控制缩醛磷脂与炎症关联的分子机制尚缺乏全面了解。然而,已经表明在炎症过程中,缩醛磷脂可能引发抗炎或促炎反应。虽然抗炎反应似乎与整个缩醛磷脂分子有关,但其促炎反应似乎与缩醛磷脂水解有关,即花生四烯酸的释放,而花生四烯酸又反过来作为产生促炎脂质介质的前体。此外,由于缩醛磷脂在人类总脂质中占很大比例,其水平的变化已被证明会改变膜特性,从而改变炎症级联反应中涉及的信号通路。通过使用缩醛磷脂替代疗法恢复缩醛磷脂水平已被证明是一种成功的抗炎策略,同时也改善了这些疾病的一些病理特征。本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以及缩醛磷脂替代疗法在治疗这些疾病中的潜在作用。