Involvement of Lipids in the Pathogenesis of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of upper and lower motor neurons. To study its underlying mechanisms, a variety of models are currently used at the cellular level and in animals with mutations in multiple ALS associated genes, including SOD1, C9ORF72, TDP-43, and FUS. Key mechanisms involved in the disease include excitotoxicity, oxidative stress, mitochondrial dysfunction, neuroinflammatory, and immune reactions.

The Sphingolipid Asset Is Altered in the Nigrostriatal System of Mice Models of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disease incurable due to late diagnosis and treatment. Therefore, one of the priorities of neurology is to study the mechanisms of PD pathogenesis at the preclinical and early clinical stages. Given the important role of sphingolipids in the pathogenesis of neurodegenerative diseases, we aimed to analyze the gene expression of key sphingolipid metabolism enzymes (ASAH1, ASAH2, CERS1, CERS3, CERS5, GBA1, SMPD1, SMPD2, UGCG) and the content of 32 sphingolipids (subspecies of ceramides, sphingomyelins, monohexosylceramides and sphinganine, sphingosine, and sphingosine-1-phosphate) in the nigrostriatal system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models of the preclinical and clinical stages of PD.

[The role of sphingolipids in pathogenesis of amyotrophic lateral sclerosis].

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by selective degeneration of motor neurons of the spinal cord and motor cortex and brain stem. The key features of the course of this disease are excitotoxicity, oxidative stress, mitochondrial dysfunction, neuro-inflammatory and immune reactions. Recently, the mechanisms of programmed cell death (apoptosis), which may be responsible for the degeneration of motor neurons in this disease, have been intensively studied.

[The role of lipids in the pathogenesis of lateral amyotrophic sclerosis].

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by selective degeneration of motor neurons of the motor cortex, brain stem and brain stem. Mutations in genes coding for SOD1, C9ORF72, TDP-43, FUS and others are associated with ALS and result in abnormal processing and transport of RNA as well as changes in the dynamics of cytoskeleton. In addition, a sharp change in the metabolism of various lipid classes, including phospholipids, fatty acids, sphingolipids, etc.

The Post-Translational Modifications, Localization, and Mode of Attachment of Non-Covalently Bound Glucanosyltransglycosylases of Yeast Cell Wall as a Key to Understanding their Functioning.

Glucan linked to proteins is a natural mega-glycoconjugate (mGC) playing the central role as a structural component of a yeast cell wall (CW). Regulation of functioning of non-covalently bound glucanosyltransglycosylases (ncGTGs) that have to remodel mGC to provide CW extension is poorly understood. We demonstrate that the main ncGTGs Bgl2 and Scw4 have phosphorylated and glutathionylated residues and are represented in CW as different pools of molecules having various firmness of attachment.

Exploring Sphingolipid Implications in Neurodegeneration.

Over the past decade, it was found that relatively simple sphingolipids, such as ceramide, sphingosine, sphingosine-1-phosphate, and glucosylceramide play important roles in neuronal functions by regulating rates of neuronal growth and differentiation. Homeostasis of membrane sphingolipids in neurons and myelin is essential to prevent the loss of synaptic plasticity, cell death and neurodegeneration. In our review we summarize data about significant brain cell alterations of sphingolipids in different neurodegenerative diseases such as Alzheimer's disease, Parkinson disease, Amyotrophic Lateral Sclerosis, Gaucher's, Farber's diseases, etc.

Changes in the Metabolism of Sphingoid Bases in the Brain and Spinal Cord of Transgenic FUS(1-359) Mice, a Model of Amyotrophic Lateral Sclerosis.

The aim of this study was to evaluate changes in the content of sphingoid bases - sphingosine (SPH), sphinganine, and sphingosine-1-phosphate (SPH-1-P) - and in expression of genes encoding enzymes involved in their metabolism in the brain structures (hippocampus, cortex, and cerebellum) and spinal cord of transgenic FUS(1-359) mice. FUS(1-359) mice are characterized by motor impairments and can be used as a model of amyotrophic lateral sclerosis (ALS). Lipids from the mouse brain structures and spinal cord after 2, 3, and 4 months of disease development were analyzed by chromatography/mass spectrometry, while changes in the expression of the SPHK1, SPHK2, SGPP2, SGPL1, ASAH1, and ASAH2 genes were assayed using RNA sequencing.

[Participation of Sphingolipids in the Pathogenesis of Atherosclerosis].

Lipid metabolism disorders are the most significant risk factor of development of cardiovascular diseases (CVD). In the process of diagnosing ischemic heart disease and other cardiovascular pathologies, levels of total cholesterol, low- and high- density lipoprotein cholesterol, triglycerides are determined. However, in recent years, close attention has been paid to the intersection of the metabolic pathways of the biosynthesis of cholesterol and sphingolipids.

[The role of sphingolipids in cardiovascular pathologies].

Cardiovascular diseases (CVD) remain the leading cause of death in industrialized countries. One of the most significant risk factors for atherosclerosis is hypercholesterolemia. Its diagnostics is based on routine lipid profile analysis, including the determination of total cholesterol, low and high density lipoprotein cholesterol, and triglycerides.

[Dimebon correction of changes in phospholipid composition induced by tumor necrosis factor-alpha in experement].

Aim: To investigate the ability of the neuroprotector dimebon to prevent alterations in brain lipid metabolism caused byTNF-α.

Material And Methods: The ability of dimebon (2,8-Dimethyl-5-[2-(6-methyl-3-pyridinyl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole hydrochloride) to prevent alterations in brain lipid metabolism caused byTNF-α was studied in 65 male mice (20+2g weight). TNF-α (10 mkg/mouse), dimebon (0.

The Many Facets of Sphingolipids in the Specific Phases of Acute Inflammatory Response.

This review provides an overview on components of the sphingolipid superfamily, on their localization and metabolism. Information about the sphingolipid biological activity in cell physiopathology is given. Recent studies highlight the role of sphingolipids in inflammatory process.

[Tumor necrosis faсtor-alpha - potential target for neuroprotector dimebon].

Dimebon (Dimebolin) is an antihistamine drug which has been used in Russia since 1983. Recently Dimebolin has attracted renewed interest after being shown to have positive effects on persons suffering from Alzheimer's disease. Animal studies have shown that dimebon acts through multiple mechanisms, both blocking the action of neurotoxic beta-amyloid peptides and inhibiting L-type calcium channels, modulating the action of AMPA and NMDA glutamate receptors.

Interaction of the nitric oxide signaling system with the sphingomyelin cycle and peroxidation on transmission of toxic signal of tumor necrosis factor-α in ischemia-reperfusion.

This review discusses the functional role of nitric oxide in ischemia-reperfusion injury and mechanisms of signal transduction of apoptosis, which accompanies ischemic damage to organs and tissues. On induction of apoptosis an interaction is observed of the nitric oxide signaling system with the sphingomyelin cycle, which is a source of a proapoptotic agent ceramide. Evidence is presented of an interaction of the sphingomyelin cycle enzymes and ceramide with nitric oxide and enzymes synthesizing nitric oxide.

Relationship between parameters of lipid peroxidation during obstructive jaundice and after bile flow restoration.

Restoration of bile flow after 9-day cholestasis in rat liver normalized the content of lipid peroxidation products. The removal of the cholestatic factor after 12-day cholestasis was not followed by recovery of these parameters. We showed that measurement of serum concentration of lipid peroxidation products in patients with cholelithiasis during the preoperative period holds promise for selection of the optimum time for surgical treatment and prediction of the risk of postoperative complications.

The relation between sphingomyelinase activity, lipid peroxide oxidation and NO-releasing in mice liver and brain.

We used animal models to study connection between oxidating system and sphingomyelin signaling cascade, because this models are more close related to people disease. Activation of n-sphingomyelinase (n-SMase) in mice liver and brain is coincided in time with increased level of peroxide products (conjugated dienes) after injection of tumor necrosis factor alpha (TNF-alpha). We found that ceramide can induce peroxide oxidation and lead to accumulation of TNF-alpha in animal organs.

Connection of lipid peroxide oxidation with the sphingomyelin pathway in the development of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by progressive decline in cognition, memory and intellect. It has been hypothesized that amyloid-beta peptide (A-beta) may have a prominent role in neurodegeneration. Oxidative mechanisms have been implicated in this pathway.

Synthesis of lipids in isolated nuclei from rat thymus and liver cells.

Synthesis of lipids was studied in isolated nuclei from rat thymus and liver cells. On incubation of the isolated nuclei with [2-14C]acetate and [1-14C]glycerol, the label was intensively incorporated into phospholipids and with a significantly lower intensity into fatty acids and cholesterol. Only trace amounts of radioactivity were detected in the lipids of chromatin prepared from isolated thymus nuclei after their incubation, and this suggested that lipids were mainly synthesized on the nuclear membrane.

Role of tumor necrosis factor alpha and sphingomyelin cycle activation in the induction of apoptosis by ischemia/reperfusion of the liver.

The signal transduction pathways triggering apoptotic mechanisms after ischemia/reperfusion may involve TNF-alpha secretion, ceramide generation, and initiation of lipid peroxidation. In the present study involvement of the TNF-alpha, sphingomyelin cycle, and lipid peroxidation in the initiation of apoptosis induced in liver cells by ischemia and reperfusion was investigated. Wistar rats were subjected to total liver ischemia (for 15, 30 min, and 1 h) followed by subsequent reperfusion.

Functional role of phospholipids in the nuclear events.

This review presents the structural and functional role of phospholipids in chromatin and nuclear matrix as well as the difference in composition and turnover compared to those present in the nuclear membrane. Nuclei have a very active lipid metabolism which seems to play an important role in the transduction of the signals to the genome in response to agonists acting at the plasma membrane level. The evidence on the presence of phospholipid-calcium-dependent protein kinase C (PKC) in nuclei and enzymes of phospholipids turnover is given.

Effects of reduced and oxidized glutathione on sphingomyelinase activity and contents of sphingomyelin and lipid peroxidation products in murine liver.

Like the phosphatidyl inositol cycle, the sphingomyelin cycle produces a series of the secondary messengers transmitting extracellular signals from the cytoplasmic membrane into the nucleus. Sphingomyelin, ceramide, sphingosine, sphingomyelinase, and ceramidase are the main components of the sphingomyelin cycle. In spite of numerous data on the functional properties of sphingomyelin cycle products, the activation mechanism for the key enzyme of the sphingomyelin cycle, sphingomyelinase (SMase), is not well understood.

Effect of bilirubin on lipid peroxidation, sphingomyelinase activity, and apoptosis induced by sphingosine and UV irradiation.

The effect of bilirubin (BR) on sphingomyelin cycle activity, lipid peroxidation (LPO), and apoptosis induced by sphingosine and UV irradiation has been studied in vivo. Neutral Mg(2+)-dependent sphingomyelinase (SMase) activity and LPO level were monitored in heart, kidney, and liver of mice after administration of BR. BR inhibited both LPO and SMase activities in heart and kidney.

Sphingolipids of transplantable rat nephroma-RA.

Contents of sphingolipids (ceramide, sphingomyelin, gangliosides) and the composition of their sphingoid bases were studied in the transplantable rat nephroma-RA and in rat kidneys. The content of sphingomyelin was about 1.3-fold decreased and the content of ceramide was about 1.