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Nutrition (Burbank, Los Angeles County,... Jun 2015The aim of this study was to assess the roles and importance of phosphatidylserine (PS), an endogenous phospholipid and dietary nutrient, in human brain biochemistry,... (Review)
Review
OBJECTIVE
The aim of this study was to assess the roles and importance of phosphatidylserine (PS), an endogenous phospholipid and dietary nutrient, in human brain biochemistry, physiology, and function.
METHODS
A scientific literature search was conducted on MEDLINE for relevant articles regarding PS and the human brain published before June 2014. Additional publications were identified from references provided in original papers; 127 articles were selected for inclusion in this review.
RESULTS
A large body of scientific evidence describes the interactions among PS, cognitive activity, cognitive aging, and retention of cognitive functioning ability.
CONCLUSION
Phosphatidylserine is required for healthy nerve cell membranes and myelin. Aging of the human brain is associated with biochemical alterations and structural deterioration that impair neurotransmission. Exogenous PS (300-800 mg/d) is absorbed efficiently in humans, crosses the blood-brain barrier, and safely slows, halts, or reverses biochemical alterations and structural deterioration in nerve cells. It supports human cognitive functions, including the formation of short-term memory, the consolidation of long-term memory, the ability to create new memories, the ability to retrieve memories, the ability to learn and recall information, the ability to focus attention and concentrate, the ability to reason and solve problems, language skills, and the ability to communicate. It also supports locomotor functions, especially rapid reactions and reflexes.
Topics: Aging; Blood-Brain Barrier; Brain; Cognition; Cognition Disorders; Dietary Supplements; Humans; Memory; Phosphatidylserines
PubMed: 25933483
DOI: 10.1016/j.nut.2014.10.014 -
Nature Reviews. Immunology Sep 2019Tissue macrophages rapidly recognize and engulf apoptotic cells. These events require the display of so-called eat-me signals on the apoptotic cell surface, the most... (Review)
Review
Tissue macrophages rapidly recognize and engulf apoptotic cells. These events require the display of so-called eat-me signals on the apoptotic cell surface, the most fundamental of which is phosphatidylserine (PtdSer). Externalization of this phospholipid is catalysed by scramblase enzymes, several of which are activated by caspase cleavage. PtdSer is detected both by macrophage receptors that bind to this phospholipid directly and by receptors that bind to a soluble bridging protein that is independently bound to PtdSer. Prominent among the latter receptors are the MER and AXL receptor tyrosine kinases. Eat-me signals also trigger macrophages to engulf virus-infected or metabolically traumatized, but still living, cells, and this 'murder by phagocytosis' may be a common phenomenon. Finally, the localized presentation of PtdSer and other eat-me signals on delimited cell surface domains may enable the phagocytic pruning of these 'locally dead' domains by macrophages, most notably by microglia of the central nervous system.
Topics: Animals; Antigens, Surface; Apoptosis; Humans; Macrophages; Membrane Proteins; Milk Proteins; Phagocytosis; Phosphatidylserines; Receptor Protein-Tyrosine Kinases; c-Mer Tyrosine Kinase
PubMed: 31019284
DOI: 10.1038/s41577-019-0167-y -
Progress in Lipid Research Oct 2014Phosphatidylserine (PS) is the major anionic phospholipid class particularly enriched in the inner leaflet of the plasma membrane in neural tissues. PS is synthesized... (Review)
Review
Phosphatidylserine (PS) is the major anionic phospholipid class particularly enriched in the inner leaflet of the plasma membrane in neural tissues. PS is synthesized from phosphatidylcholine or phosphatidylethanolamine by exchanging the base head group with serine, and this reaction is catalyzed by phosphatidylserine synthase 1 and phosphatidylserine synthase 2 located in the endoplasmic reticulum. Activation of Akt, Raf-1 and protein kinase C signaling, which supports neuronal survival and differentiation, requires interaction of these proteins with PS localized in the cytoplasmic leaflet of the plasma membrane. Furthermore, neurotransmitter release by exocytosis and a number of synaptic receptors and proteins are modulated by PS present in the neuronal membranes. Brain is highly enriched with docosahexaenoic acid (DHA), and brain PS has a high DHA content. By promoting PS synthesis, DHA can uniquely expand the PS pool in neuronal membranes and thereby influence PS-dependent signaling and protein function. Ethanol decreases DHA-promoted PS synthesis and accumulation in neurons, which may contribute to the deleterious effects of ethanol intake. Improvement of some memory functions has been observed in cognitively impaired subjects as a result of PS supplementation, but the mechanism is unclear.
Topics: Animals; Biosynthetic Pathways; Brain; Cell Differentiation; Cell Survival; Docosahexaenoic Acids; Humans; Models, Biological; Neurons; Phosphatidylserines
PubMed: 24992464
DOI: 10.1016/j.plipres.2014.06.002 -
Nature Reviews. Molecular Cell Biology Aug 2023Cellular membranes function as permeability barriers that separate cells from the external environment or partition cells into distinct compartments. These membranes are... (Review)
Review
Cellular membranes function as permeability barriers that separate cells from the external environment or partition cells into distinct compartments. These membranes are lipid bilayers composed of glycerophospholipids, sphingolipids and cholesterol, in which proteins are embedded. Glycerophospholipids and sphingolipids freely move laterally, whereas transverse movement between lipid bilayers is limited. Phospholipids are asymmetrically distributed between membrane leaflets but change their location in biological processes, serving as signalling molecules or enzyme activators. Designated proteins - flippases and scramblases - mediate this lipid movement between the bilayers. Flippases mediate the confined localization of specific phospholipids (phosphatidylserine (PtdSer) and phosphatidylethanolamine) to the cytoplasmic leaflet. Scramblases randomly scramble phospholipids between leaflets and facilitate the exposure of PtdSer on the cell surface, which serves as an important signalling molecule and as an 'eat me' signal for phagocytes. Defects in flippases and scramblases cause various human diseases. We herein review the recent research on the structure of flippases and scramblases and their physiological roles. Although still poorly understood, we address the mechanisms by which they translocate phospholipids between lipid bilayers and how defects cause human diseases.
Topics: Humans; Lipid Bilayers; Phospholipids; Cell Membrane; Glycerophospholipids; Phosphatidylserines
PubMed: 37106071
DOI: 10.1038/s41580-023-00604-z -
Current Opinion in Cell Biology Aug 2023Phosphatidylserine (PS) is a negatively charged glycerophospholipid found mainly in the plasma membrane (PM) and in the late secretory/endocytic compartments, where it... (Review)
Review
Phosphatidylserine (PS) is a negatively charged glycerophospholipid found mainly in the plasma membrane (PM) and in the late secretory/endocytic compartments, where it regulates cellular activity and can mediate apoptosis. Export of PS from the endoplasmic reticulum, its site of synthesis, to other compartments, and its transbilayer asymmetry must therefore be precisely regulated. We review recent findings on nonvesicular transport of PS by lipid transfer proteins (LTPs) at membrane contact sites, on PS flip-flop between membrane leaflets by flippases and scramblases, and on PS nanoclustering at the PM. We also discuss emerging data on cooperation between scramblases and LTPs, how perturbation of PS distribution can lead to disease, and the specific role of PS in viral infection.
Topics: Phosphatidylserines; Cell Membrane; Biological Transport; Endoplasmic Reticulum; Mitochondrial Membranes
PubMed: 37413778
DOI: 10.1016/j.ceb.2023.102192 -
Cellular Immunology Feb 2023Phosphatidylserine (PS) is an anionic phospholipid exposed on the surface of apoptotic cells. The exposure of PS typically recruits and signals phagocytes to engulf and...
Phosphatidylserine (PS) is an anionic phospholipid exposed on the surface of apoptotic cells. The exposure of PS typically recruits and signals phagocytes to engulf and silently clear these dying cells to maintain tolerance via immunological ignorance. However, recent and emerging evidence has demonstrated that PS converts an "immunogen" into a "tolerogen", and PS exposure on the surface of cells or vesicles actively promotes a tolerogenic environment. This tolerogenic property depends on the biophysical characteristics of PS-containing vesicles, including PS density on the particle surface to effectively engage tolerogenic receptors, such as TIM-4, which is exclusively expressed on the surface of antigen-presenting cells. We harnessed the cellular and molecular mechanistic insight of PS-mediated immune regulation to design an effective oral tolerance approach. This immunotherapy has been shown to prevent/reduce immune response against life-saving protein-based therapies, food allergens, autoantigens, and the antigenic viral capsid peptide commonly used in gene therapy, suggesting a broad spectrum of potential clinical applications. Given the good safety profile of PS together with the ease of administration, oral tolerance achieved with PS-based nanoparticles has a very promising therapeutic impact.
Topics: Phosphatidylserines; Immunotherapy; Antigen-Presenting Cells; Autoantigens; Immune Tolerance; Apoptosis
PubMed: 36586393
DOI: 10.1016/j.cellimm.2022.104660 -
BioEssays : News and Reviews in... Dec 2022The asymmetric distribution of lipids, maintained by flippases/floppases and scramblases, plays a pivotal role in various physiologic processes. Scramblases are proteins... (Review)
Review
The asymmetric distribution of lipids, maintained by flippases/floppases and scramblases, plays a pivotal role in various physiologic processes. Scramblases are proteins that move phospholipids between the leaflets of the lipid bilayer of the cellular membrane in an energy-independent manner. Recent studies have indicated that viral infection is closely related to cellular lipid distribution. The level and distribution of phosphatidylserine (PtdSer) in cells have been demonstrated to be critical regulators of viral infections. Previous studies have supported that the infection of human immunodeficiency virus (HIV), Zika virus, Ebola virus (EBOV), influenza virus, and dengue fever virus require the externalization of phospholipids mediated by scramblases, which are also involved in the pathogenicity of the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, we review the relationship of scramblases with viruses and the potential viral effector proteins that might utilize host scramblases.
Topics: Humans; SARS-CoV-2; COVID-19; Phosphatidylserines; Phospholipids; Virus Diseases; Zika Virus; Zika Virus Infection
PubMed: 36285664
DOI: 10.1002/bies.202100261 -
Critical Reviews in Biochemistry and... Apr 2020P4-ATPases, a subfamily of P-type ATPases, translocate cell membrane phospholipids from the exoplasmic/luminal leaflet to the cytoplasmic leaflet to generate and... (Review)
Review
P4-ATPases, a subfamily of P-type ATPases, translocate cell membrane phospholipids from the exoplasmic/luminal leaflet to the cytoplasmic leaflet to generate and maintain membrane lipid asymmetry. Exposure of phosphatidylserine (PS) in the exoplasmic leaflet is well known to transduce critical signals for apoptotic cell clearance and platelet coagulation. PS exposure is also involved in many other biological processes, including myoblast and osteoclast fusion, and the immune response. Moreover, mounting evidence suggest that PS exposure is critical for neuronal regeneration and degeneration. In apoptotic cells, PS exposure is induced by irreversible activation of scramblases and inactivation of P4-ATPases. However, how PS is reversibly exposed and restored in viable cells during other biological processes remains poorly understood. In the present review, we discuss the physiological significance of reversible PS exposure in living cells, and the putative roles of flippases, floppases, and scramblases.
Topics: Animals; Apoptosis; Cell Membrane; Cell Survival; Cytoplasm; Humans; Lipid Bilayers; P-type ATPases; Phosphatidylserines; Phospholipid Transfer Proteins; Platelet Activation; Substrate Specificity
PubMed: 32408772
DOI: 10.1080/10409238.2020.1758624 -
Current Opinion in Lipidology Aug 2016It is now widely acknowledged that phosphatidylserine is a multifunctional bioactive lipid. In this review, we focus on the function of phosphatidylserine in modulating... (Review)
Review
PURPOSE OF REVIEW
It is now widely acknowledged that phosphatidylserine is a multifunctional bioactive lipid. In this review, we focus on the function of phosphatidylserine in modulating cholesterol metabolism, influencing inflammatory response and regulating coagulation system, and discuss promising phosphatidylserine-based therapeutic approaches and detection techniques in atherosclerosis.
RECENT FINDINGS
Phosphatidylserine has been suggested to play important roles in physiological processes, such as apoptosis, inflammation, and coagulation. Recent data demonstrate atheroprotective potential of phosphatidylserine, reflecting its capacity to inhibit inflammation, modulate coagulation, and enhance HDL functionality. Furthermore, modern lipidomic approaches have enabled the investigation of phosphatidylserine properties relevant to the lipid-based drug delivery and development of reconstituted HDL.
SUMMARY
Studies of phosphatidylserine in relation to atherosclerosis represent an area of opportunity. Additional research elucidating mechanisms underlying experimentally observed atheroprotective effects of phosphatidylserine is required to fully explore therapeutic potential of this naturally occurring phospholipid in cardiovascular disease.
Topics: Atherosclerosis; Blood Coagulation; Cholesterol; Humans; Inflammation; Phosphatidylserines
PubMed: 27070078
DOI: 10.1097/MOL.0000000000000298 -
Proceedings of the National Academy of... Nov 2018
Topics: Macrophages; Phosphatidylserines; Phospholipids; Precursor Cells, B-Lymphoid
PubMed: 30446613
DOI: 10.1073/pnas.1817485115