Изменение Метаболизма Сфингоидных Оснований В Структурах Головного И Спинного Мозга Трансгенных Мышей Линии Fus(1-359), Моделирующих Боковой Амиотрофический Склероз

Gutner, U. A.; Shupik, M. A.; Малошицкая, О.А.; Соколов, С.А.; Резвых, А.П.; Фуников, С.Ю.; Лебедев, А.Т.; Устюгов, А.А.; Алесенко, А.В.

doi:10.1134/s0320972519100063

Cited by 1 publication

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“…Expression of SK-1 and SK-2 and the content of some molecular species of ceramides and sphingosine correlate with the degree of disease severity [107] An increase in the expression of S1P lyase, a decrease in the expression of S1P phosphatase [108] tions of sphingomyelin metabolism, complex sphingolipids can be a source of ceramide.…”

Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

“…Using a model of ALS in a FUS transgenic mouse line, Gutner at al. showed that, at the terminal stage of the development of the disease, significant changes in the expression of the genes of S1P metabolism occur in the spinal cord: an increase in the expression of S1P lyase and a decrease in the expression of S1P phosphatase (2019) [108]. In this case, the content of sphingosine and sphinganine increases; correspondingly, the S1P-to-sphingosine/sphinganine ratio changes, which may be a manifestation of intensive development of apoptosis in the cells of the spinal cord.…”

Section: S1p and Amyotrophicmentioning

confidence: 99%

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The Role of Sphingosine-1-Phosphate in Neurodegenerative Diseases

Gutner

Shupik

2021

Russ J Bioorg Chem

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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).

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Section: Amyotrophic Lateral Sclerosismentioning

confidence: 99%

Section: S1p and Amyotrophicmentioning

confidence: 99%