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. It has been shown that in PD models, the expression of five of the nine studied genes (CERS1, CERS5, ASAH1, ASAH2, and GBA1) increases but only in the substantia nigra (SN) containing dopaminergic cell bodies. Changes in the expression of enzyme genes were accompanied by an increase in the content of 7 of the 32 studied sphingolipids. Such findings suggest these genes as attractive candidates for diagnostic purposes for preclinical and clinical stages of PD.

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. In addition, significant metabolism alterations of various lipids classes, including phospholipids, fatty acids, sphingolipids, and others have been increasingly recognized. Recently, the mechanisms of programmed cell death (apoptosis), which may be responsible for the degeneration of motor neurons observed in the disease, have been intensively studied. In this context, sphingolipids, which are the most important sources of secondary messengers transmitting signals for cell proliferation, differentiation, and apoptosis, are gaining increasing attention in the context of ALS pathogenesis given their role in the development of neuroinflammatory and immune responses. This review describes changes in lipids content and activity of enzymes involved in their metabolism in ALS, both summarizing current evidence from animal models and clinical studies and discussing the potential of new drugs among modulators of lipid metabolism enzymes.

Development of modern methods for metabolome assessment, such as gas chromatography–mass spectrometry, allows one to expand the knowledge about the features of lipid metabolism in various clinical conditions. The study was aimed to investigate lipidome features in patients with different probability of family hypercholesterolemia (FH). The study involved 35 patients: 15 men (42.9%) and 20 women (57.1%) with dislipidemia or early cardiovascular diseases which manifested below 55 in men and 60 in women (average age of patients was 49.8 ± 9.96). The family dislipidemia probability was evaluated using the Dutch Lipid Clinic Network Score. In 10 patients the probability of FH was low (score 1–2), 22 patients had possible FH (score 3–5). Three patients had probable or definite FH (score 6 in 2 patients, score 9 in one patient). Determination of molecular species of sphingomyelins, ceramides and sphingoid bases (sphingosine, sphinganine) as well as galactosylceramide was carried out using gas chromatography–mass spectrometry. In patients with definite/probable FH the sphingosine level was significantly higher compared with patients having low probability of FH (144.36 ± 107.863 and 50.14 ± 62.409 ng/ml; р = 0.01). In patients with FH, an increase in the proportion of long chain sphingomyelin SM 18 : 1/22 : 0 as well as a significant increase in the level of long chain ceramides with С 20 : 1 and С 22 : 1 was determined. Positive correlation of low-density lipoproteins and sphingosine level (r = 0.344; p = 0.047) together with negative correlation of high-density lipoproteins (HDL), sphinganine (r = –0.52; p = 0.002), and galactosylceramide level (r = –0.56; p = 0.001) were detected. Thus, in patients with high probability of FH the lipidome changes were observed, which could be considered the cardiovascular risk markers.

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., was detected. This review describes changes in lipid content and activity of enzymes involved in their metabolism in ALS animal models as well as in patients. Changes in the metabolism of fatty acids, phospholipids, cholesterol and its derivatives are reviewed in detail. The prospects of searching for new drugs among modulators of lipid metabolism enzymes are discussed.

Sphingosine-1-phosphate (S1P) is a biologically active sphingolipid metabolite with antiapoptotic action. As a signal molecule, S1P regulates the survival of cells and their differentiation, the motility and dynamics of the cytoskeleton and is involved in the processes of cell migration, proliferation, and autophagy. The content of S1P in the cell is controlled by specific kinases and phosphatases as well as the enzyme of S1P degradation, S1P lyase. S1P fulfils most of its functions as a ligand to specific membrane G-protein-coupled receptors (S1PR_1–5). S1P receptors are expressed by all cell types, including neurons and glial cells. In the central nervous system (CNS), S1P can perform protective functions and induce survival-stimulating signaling pathways or, conversely, contribute to the development of pathological processes, including neurodegenerative disorders. The functions of S1P, the expression of its receptors, and their action depend on the type of CNS cells, the stage of their development, and the state of the whole organism. Based on the action of S1P, the drug fingolimod was developed, which, by binding to S1P receptors with high affinity, diminishes the inflammatory cell infiltration, damage to tissues, and demyelination. The review highlights recent advances in the understanding of how S1P acts and its role in neurodegenerative disorders (Alzheimer’s disease, Parkinson’s disease, and lateral amyotrophic sclerosis).

Background: The aim of our study was to determine the role of sphingolipids, which control proliferation and apoptosis, in the placenta of pregnant women with pregnancy-associated breast cancer (PABC) after chemotherapy compared with healthy patients. Methods: We analyzed (by the PCR method) the gene expression of key sphingolipid metabolism enzymes (sphingomyelinases (SMPD1 and SMPD3), acid ceramidase (ASAH1), ceramide synthases (CERS 1–6), sphingosine kinase1 (SPHK1), sphingosine-1-phosphate lyase 1 (SGPL1), and sphingosine-1-phosphate receptors (S1PR1, S1PR2, and S1PR3)) and the content of subspecies of ceramides, sphingosine, and sphingosine-1-phosphate in seven patients with PABC after chemotherapy and eight healthy pregnant women as a control group. Results: We found a significant increase in the expression of genes of acid ceramidase (ASAH1), sphingosine-1-phosphate lyase 1 (SGPL1), sphingosine kinase (SPHK1), and ceramide synthases (CERS 1-3, 5, 6) in the samples of patients with PABC during their treatment with cytostatic chemotherapy. The increase in the expression of the enzymes’ genes was not accompanied by changes in the content of the studied sphingolipids. Such significant changes in the expression of genes controlling the level of CER, sphingosine, and S1P may indicate their ability to initiate the metabolism of pro-apoptotic and anti-apoptotic sphingolipids in the placenta of pregnant women with cancer undergoing chemotherapy in order to maintain levels typical of the placenta of healthy women. Conclusions: Our results may indicate the promising mechanism of placenta protection during chemotherapy for pregnant women with breast cancer and, consequently, of the newborn. This protective effect of the placenta and especially for the newborn has been discovered for the first time and requires more careful study.