scholarly journals Lipid rafts and neurodegeneration: structural and functional roles in physiologic aging and neurodegenerative diseases

2019 ◽  
Vol 61 (5) ◽  
pp. 636-654 ◽  
Author(s):  
Sara Grassi ◽  
Paola Giussani ◽  
Laura Mauri ◽  
Simona Prioni ◽  
Sandro Sonnino ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Lipid Rafts ◽  
Membrane Lipids ◽  
Membrane Lipid ◽  
Lysosomal Storage ◽  
Functional Roles ◽  
Composition And Structure ◽  
Liquid Ordered ◽  
High Enrichment ◽  
And Function

Lipid rafts are small, dynamic membrane areas characterized by the clustering of selected membrane lipids as the result of the spontaneous separation of glycolipids, sphingolipids, and cholesterol in a liquid-ordered phase. The exact dynamics underlying phase separation of membrane lipids in the complex biological membranes are still not fully understood. Nevertheless, alterations in the membrane lipid composition affect the lateral organization of molecules belonging to lipid rafts. Neural lipid rafts are found in brain cells, including neurons, astrocytes, and microglia, and are characterized by a high enrichment of specific lipids depending on the cell type. These lipid rafts seem to organize and determine the function of multiprotein complexes involved in several aspects of signal transduction, thus regulating the homeostasis of the brain. The progressive decline of brain performance along with physiological aging is at least in part associated with alterations in the composition and structure of neural lipid rafts. In addition, neurodegenerative conditions, such as lysosomal storage disorders, multiple sclerosis, and Parkinson’s, Huntington’s, and Alzheimer’s diseases, are frequently characterized by dysregulated lipid metabolism, which in turn affects the structure of lipid rafts. Several events underlying the pathogenesis of these diseases appear to depend on the altered composition of lipid rafts. Thus, the structure and function of lipid rafts play a central role in the pathogenesis of many common neurodegenerative diseases.

scholarly journals Impact of Membrane Lipids on UapA and AzgA Transporter Subcellular Localization and Activity in Aspergillus nidulans

2021 ◽  
Vol 7 (7) ◽  
pp. 514
Author(s):  
Mariangela Dionysopoulou ◽  
George Diallinas
Keyword(s):  
Plasma Membrane ◽  
Subcellular Localization ◽  
Aspergillus Nidulans ◽  
Membrane Lipids ◽  
Membrane Lipid ◽  
Lipid Biosynthesis ◽  
Transport Kinetics ◽  
Negative Effect ◽  
And Function

Recent biochemical and biophysical evidence have established that membrane lipids, namely phospholipids, sphingolipids and sterols, are critical for the function of eukaryotic plasma membrane transporters. Here, we study the effect of selected membrane lipid biosynthesis mutations and of the ergosterol-related antifungal itraconazole on the subcellular localization, stability and transport kinetics of two well-studied purine transporters, UapA and AzgA, in Aspergillus nidulans. We show that genetic reduction in biosynthesis of ergosterol, sphingolipids or phosphoinositides arrest A. nidulans growth after germling formation, but solely blocks in early steps of ergosterol (Erg11) or sphingolipid (BasA) synthesis have a negative effect on plasma membrane (PM) localization and stability of transporters before growth arrest. Surprisingly, the fraction of UapA or AzgA that reaches the PM in lipid biosynthesis mutants is shown to conserve normal apparent transport kinetics. We further show that turnover of UapA, which is the transporter mostly sensitive to membrane lipid content modification, occurs during its trafficking and by enhanced endocytosis, and is partly dependent on autophagy and Hect-type HulARsp5 ubiquitination. Our results point out that the role of specific membrane lipids on transporter biogenesis and function in vivo is complex, combinatorial and transporter-dependent.

Manipulating membrane lipid profiles to restore T-cell function in autoimmunity

2015 ◽  
Vol 43 (4) ◽  
pp. 745-751 ◽  
Author(s):  
Kirsty E. Waddington ◽  
Elizabeth C. Jury
Keyword(s):  
T Cell ◽  
Lipid Rafts ◽  
Lupus Erythematosus ◽  
Cell Function ◽  
Immune Cell ◽  
Membrane Lipids ◽  
Membrane Lipid ◽  
Plasma Membrane Lipid ◽  
Disease Systemic Lupus Erythematosus ◽  
Acyl Chains

Plasma membrane lipid rafts are heterogeneous cholesterol and glycosphingolipid (GSL)-enriched microdomains, within which the tight packing of cholesterol with the saturated-acyl chains of GSLs creates a region of liquid-order relative to the surrounding disordered membrane. Thus lipid rafts govern the lateral mobility and interaction of membrane proteins and regulate a plethora of signal transduction events, including T-cell antigen receptor (TCR) signalling. The pathways regulating homoeostasis of membrane cholesterol and GSLs are tightly controlled and alteration of these metabolic processes coincides with immune cell dysfunction as is evident in atherosclerosis, cancer and autoimmunity. Indeed, membrane lipid composition is emerging as an important factor influencing the ability of cells to respond appropriately to microenvironmental stimuli. Consequently, there is increasing interest in targeting membrane lipids or their metabolic control as a novel therapeutic approach to modulate immune cell behaviour and our recent work demonstrates that this is a promising strategy in T-cells from patients with the autoimmune disease systemic lupus erythematosus (SLE).

Membrane lipids under norm and pathology

2021 ◽  
Vol 19 (1) ◽  
pp. 59-75
Author(s):  
Basheer Abdullah Marzoog ◽  
◽  
Tatyana Ivanovna Vlasova ◽  
Keyword(s):  
Metabolic Disorders ◽  
Membrane Lipids ◽  
Membrane Lipid ◽  
Highly Qualified ◽  
Lysosomal Storage ◽  
Permanent Disability ◽  
Highly Sensitive ◽  
Life Threatening ◽  
Different Tissues ◽  
Storage Disorders

Introduction. Lipid is an essential component of the cell and its organelles membrane. The uniqueness and selectivity of lipids to specific functions and asymmetry of lipid distribution in the organelle’s membrane give the cell ability of being highly qualified and specified. Aim. The paper provides a comprehensive review of membrane lipids in different tissues and organelles of the cell in norm and disease. Material and methods. The paper analyzed the present literature data on membrane lipids behavior in physiology and pathology. Analysis of the literature. The major structural and functional lipids of the cell membrane are phosphatidylcholine > phosphatidylethanolamine. The absence/deficiency or augmentation of a specific type of lipid results in serious defects and usually life-threatening with a permanent disability. The observations discussed here suggest, the lipid peroxidation severity depends on the membrane lipid composition of the cell. Some tissue cells can handle lipoperoxidation and protect themselves from the peroxidation damaging products better, while other cells cannot compensate. Therefore, some organs are highly sensitive to peroxidation and irreversible changes occur rapidly. Conclusion. To sum up, the understanding of lipid’s role in norm and disease is clinically crucial to evaluate a novel therapeutic target to treat many metabolic disorders such as metabolic syndrome and some lysosomal storage disorders via targeting specific new signaling pathways, lipid molecules, and enzymes.

scholarly journals Lipid rafts and regulation of the cytoskeleton during T cell activation

2005 ◽  
Vol 360 (1461) ◽  
pp. 1663-1672 ◽  
Author(s):  
Karina F Meiri
Keyword(s):  
T Cell ◽  
Lipid Rafts ◽  
T Cell Activation ◽  
Cell Activation ◽  
Immunological Synapse ◽  
Membrane Lipids ◽  
Actin Dynamics ◽  
Associated Proteins ◽  
Liquid Ordered

The ability of polarized cells to initiate and sustain directional responses to extracellular signals is critically dependent on direct communication between spatially organized signalling modules in the membrane and the underlying cytoskeleton. Pioneering work in T cells has shown that the assembly of signalling modules critically depends on the functional compartmentalization of membrane lipids into ordered microdomains or lipid rafts. The significance of rafts in T cell activation lies not only in their ability to recruit the signalling partners that eventually assemble into a mature immunological synapse but also in their ability to regulate actin dynamics and recruit cytoskeletal associated proteins, thereby achieving the structural polarization underlying stability of the synapse—a critical prerequisite for activation to be sustained. Lipid rafts vary quite considerably in size and visualizing the smallest of them in vivo has been challenging. Nonetheless it is now been shown quite convincingly that a surprisingly large proportion—in the order of 50%—of external membrane lipids (chiefly cholesterol and glycosphingolipids) can be dynamically localized in these liquid ordered rafts. Complementary inner leaflet rafts are less well characterized, but contain phosphoinositides as an important functional component that is crucial for regulating the behaviour of the actin cytoskeleton. This paper provides an overview of the interdependency between signalling and cytoskeletal polarization, and in particular considers how regulation of the cytoskeleton plays a crucial role in the consolidation of rafts and their stabilization into the immunological synapse.

Microscopy of membrane lipids: how precisely can we define their distribution?

2015 ◽  
Vol 57 ◽  
pp. 81-91 ◽  
Author(s):  
Sho Takatori ◽  
Toyoshi Fujimoto
Keyword(s):  
Membrane Lipids ◽  
Freeze Fracture ◽  
Practical Method ◽  
Membrane Lipid ◽  
Electron Microscopic ◽  
Functional Roles ◽  
Lipid Dynamics ◽  
Lipid Species ◽  
Quick Freezing ◽  
The Moment

Membrane lipids form the basic framework of biological membranes by forming the lipid bilayer, but it is becoming increasingly clear that individual lipid species play different functional roles. However, in comparison with proteins, relatively little is known about how lipids are distributed in the membrane. Several microscopic methods are available to study membrane lipid dynamics in living cells, but defining the distribution of lipids at the submicrometre scale is difficult, because lipids diffuse quickly in the membrane and most lipids do not react with aldehydes that are commonly used as fixatives. Quick-freezing appears to be the only practical method by which to stop the lipid movement instantaneously and capture the molecular localization at the moment of interest. Electron microscopic methods, using cryosections, resin sections, and freeze-fracture replicas are used to visualize lipids in quick-frozen samples. The method that employs the freeze-fracture replica is unique in that it requires no chemical treatment and provides a two-dimensional view of the membrane.

scholarly journals Lipids in Pathophysiology and Development of the Membrane Lipid Therapy: New Bioactive Lipids

Membranes ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 919
Author(s):  
Manuel Torres ◽  
Sebastià Parets ◽  
Javier Fernández-Díaz ◽  
Roberto Beteta-Göbel ◽  
Raquel Rodríguez-Lorca ◽  
...  
Keyword(s):  
Lipid Bilayer ◽  
Lipid Composition ◽  
Membrane Lipids ◽  
Therapeutic Potential ◽  
Membrane Lipid ◽  
Fatty Acyl ◽  
Bioactive Lipids ◽  
Membrane Lipid Composition ◽  
Membrane Structure And Function ◽  
And Function

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).

scholarly journals Membrane lipid rafts and neurobiology: age-related changes in membrane lipids and loss of neuronal function

2015 ◽  
Vol 594 (16) ◽  
pp. 4565-4579 ◽  
Author(s):  
Junji Egawa ◽  
Matthew L. Pearn ◽  
Brian P. Lemkuil ◽  
Piyush M. Patel ◽  
Brian P. Head
Keyword(s):  
Lipid Rafts ◽  
Membrane Lipids ◽  
Membrane Lipid ◽  
Neuronal Function ◽  
Age Related ◽  
Age Related Changes

scholarly journals Searching for MIND: MicroRNAs in Neurodegenerative Diseases

2009 ◽  
Vol 2009 ◽  
pp. 1-8 ◽  
Author(s):  
Christian Barbato ◽  
Francesca Ruberti ◽  
Carlo Cogoni
Keyword(s):  
Neurodegenerative Diseases ◽  
Neural Development ◽  
Molecular Mechanisms ◽  
Brain Diseases ◽  
Mirna Biogenesis ◽  
Regulate Gene Expression ◽  
Functional Roles ◽  
Potential Development ◽  
New Frontier ◽  
And Function

In few years our understanding of microRNA (miRNA) biogenesis, molecular mechanisms by which miRNAs regulate gene expression, and the functional roles of miRNAs has been expanded. Interestingly, numerous miRNAs are expressed in a spatially and temporally controlled manner in the nervous system, suggesting that their posttrascriptional regulation may be particularly relevant in neural development and function. MiRNA studies in neurobiology showed their involvement in synaptic plasticity and brain diseases. In this review ,correlations between miRNA-mediated gene silencing and Alzheimer's, Parkinson's, and other neurodegenerative diseases will be discussed. Molecular and cellular neurobiological studies of the miRNAs in neurodegeneration represent the exploration of a new Frontier of miRNAs biology and the potential development of new diagnostic tests and genetic therapies for neurodegenerative diseases.

Lipid Metabolism as a Site of Herbicide Action

Weed Science ◽  
1973 ◽  
Vol 21 (5) ◽  
pp. 477-480 ◽  
Author(s):  
J. B. St. John ◽  
J. L. Hilton
Keyword(s):  
Membrane Lipids ◽  
Lipid Synthesis ◽  
Membrane Lipid ◽  
Cell Membrane Permeability ◽  
Glyceride Synthesis ◽  
Membrane Structure And Function ◽  
And Function ◽  
A Site

Dinoseb (2-sec-butyl-4,6-dinitrophenol) and MBR 8251 [1,1 1-trifluoro-4′-(phenylsulfonyl)-methanesulfono-o-toluidide] inhibited enzymic synthesis of glycerides in vitro. The physiological significance of this inhibition was confirmed in intact wheat [Triticum aestivumL., ‘Mediterranean’ (C.I. 5303)] seedlings; dinoseb and MBR 8251 inhibition of glyceride synthesis in vivo was evidenced by a buildup in free fatty acids and a decrease in neutral and polar lipids. Glyceride synthesis and growth were reduced approximately equally by dinoseb and MBR 8251. However, polar (membrane) lipids were reduced more drastically than growth. It is suggested that dinoseb and MBR 8251 alter membrane structure and function through an inhibition of membrane lipid synthesis. DNP (dinitrophenol) was only slightly inhibitory in either the in vitro or in vivo system. Dinoseb was more effective than MBR 8251 in destruction of cell membrane permeability of intact roots immediately after treatment.

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