Abstract
Membranes are mainly composed of a lipid bilayer and proteins, constituting a checkpoint for the entry and passage of signals and other molecules. Their composition can be modulated by diet, pathophysiological processes, and nutritional/pharmaceutical interventions. In addition to their use as an energy source, lipids have important structural and functional roles, e.g., fatty acyl moieties in phospholipids have distinct impacts on human health depending on their saturation, carbon length, and isometry. These and other membrane lipids have quite specific effects on the lipid bilayer structure, which regulates the interaction with signaling proteins. Alterations to lipids have been associated with important diseases, and, consequently, normalization of these alterations or regulatory interventions that control membrane lipid composition have therapeutic potential. This approach, termed membrane lipid therapy or membrane lipid replacement, has emerged as a novel technology platform for nutraceutical interventions and drug discovery. Several clinical trials and therapeutic products have validated this technology based on the understanding of membrane structure and function. The present review analyzes the molecular basis of this innovative approach, describing how membrane lipid composition and structure affects protein-lipid interactions, cell signaling, disease, and therapy (e.g., fatigue and cardiovascular, neurodegenerative, tumor, infectious diseases).
Highlights
The human body is made up of trillions of cells that work in a coordinated manner.In this context, health problems originated due to cellular alterations that affect physiological processes [1], and these alterations may induce malfunctions and/or abnormal levels of macromolecules, metabolites, hormones, etc
Referred to as lipid replacement (LRT) [4] or membrane lipid therapy (MLT or melitherapy) [3], a number of different therapeutic strategies fall under this umbrella, each sharing the common feature of regulating cell physiology by provoking relevant changes to the plasma membrane (PM)
This review describes the critical roles of lipids in biological membranes, their involvement in pathophysiological processes, and the development of therapies focused on membrane lipid regulation and/or replacement
Summary
The human body is made up of trillions of cells that work in a coordinated manner. In this context, health problems originated due to cellular alterations that affect physiological processes [1], and these alterations may induce malfunctions and/or abnormal levels of macromolecules, metabolites, hormones, etc. Changes in the membrane lipid composition or structure can dramatically alter proteinlipid interactions, including those that are involved in the translocation of proteins to or from the membrane to shape the signals at this cell barrier. Lipids with a structure resembling an inverted cone (e.g., lysophospholipids) or a truncated cone with a small polar head phosphatidylethanolamine (PE) or diacylglycerol (DAG) induce curvature in the membrane, forming nonlamellar phases [14] These phases are rare in healthy cells, and they can be organized into hexagonal (HI or HII ) or cubic phases [12], representing preferential sites for the localization of specific signaling proteins involved in different biological processes such as budding and fusion/fission [3,15,16,17,18].
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