iMed.ULisboa - Research Institute for Medicines, Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal.
Centro de Química-Física Molecular and IBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisbon, Portugal.
Adv Exp Med Biol. 2019;1159:79-108. doi: 10.1007/978-3-030-21162-2_6.
Ceramides are the central molecules in sphingolipid metabolism. In addition, they are recognized as important modulators of cell function, playing key roles in several cellular processes that range from cell proliferation to cell death. Moreover, ceramides were implicated in multiple diseases, including cancer, neurodegenerative and metabolic diseases, and also in infection by different pathogens. The mechanisms underlying the diverse biological and pathological actions of ceramides are yet to be fully elucidated. Several lines of evidence suggest that the structural features of ceramides, namely their high hydrophobicity and ability to establish strong H-bond network, are responsible for changes in the biophysical properties of biological membranes that can affect the activity of proteins and activate signaling pathways. Ceramide-induced alterations in membrane biophysical properties might also influence the internalization, trafficking and sorting of lipids, proteins, drugs and even pathogens contributing to cell pathophysiology. In this chapter, we critically discuss the ability of ceramides to form lipid domains with atypical biophysical properties and how these domains can be involved in those processes.
神经酰胺是神经鞘脂代谢中的核心分子。此外，它们被认为是细胞功能的重要调节剂，在从细胞增殖到细胞死亡的多种细胞过程中发挥关键作用。此外，神经酰胺还与多种疾病有关，包括癌症、神经退行性和代谢性疾病，以及不同病原体的感染。神经酰胺的多种生物学和病理学作用的机制尚待充分阐明。有几条证据表明，神经酰胺的结构特征，即其高疏水性和形成强氢键网络的能力，负责改变生物膜的生物物理特性，从而影响蛋白质的活性并激活信号通路。神经酰胺诱导的膜生物物理性质的改变也可能影响脂质、蛋白质、药物甚至病原体的内化、运输和分拣，从而导致细胞病理生理学的改变。在这一章中，我们批判性地讨论了神经酰胺形成具有非典型生物物理特性的脂质域的能力，以及这些域如何参与这些过程。
