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

Gutner, U. A.; Shupik, M. A.; Maloshitskaya, O. A.; Sokolov, Sergey; Rezvykh, Alexander P.; Funikov, Sergei; Lebedev, A. T.; Ustyugov, A. A.; Alessenko, A. V.

doi:10.1134/s0006297919100055

Cited by 15 publications

(10 citation statements)

References 70 publications

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“…SphK, that lead to the synthesis of anti-apoptotic S1P, reduces Sph pool thereby saving neuronal cells from death. A pronounced dysregulation in the metabolism of sphingoid bases, including Sphn, Sph, and S1P, in transgenic FUS mice (1-359) simulating ASL, was demonstrated (101). The study provide evidence that Sphn and Sphincrease sharply mainly in the spinal cord of mice, while their content is low and practically does not change in brain structures during the development of ALS.…”

Section: Sphinganine Sphingosine and Sphingosine-1-phoshatementioning

confidence: 62%

“…Significant disturbances were also found in the expression of SphL metabolism genes at different stages of ALS, mainly in the spinal cord. The gene expression of acylsphingosine amidohydrolase 1 (Asah1) and acid Cerase (aCerase), localized in lysosomes, increases while the expression level of Asah2 and neutral Cerase (nCerase), located on the surface of the plasma membrane, significantly decreases during the progression of FUS-mediated proteinopathy (101).…”

Section: Sphinganine Sphingosine and Sphingosine-1-phoshatementioning

confidence: 99%

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Exploring Sphingolipid Implications in Neurodegeneration

Alessenko

Albi

2020

Front. Neurol.

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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. We reported results obtained in brain tissue from both animals in which diseases were induced and humans in autopsy samples. Moreover, attention was paid on sphingolipids in biofluids, liquor and blood, from patients. In Alzheimer's disease sphingolipids are involved in the processing and aggregation of β-amyloid and in the transmission of the cytotoxic signal β-amyloid and TNFα-induced. Recently, the gangliosides metabolism in transgenic animals and the relationship between blood sphingolipids changes and cognitive impairment in Alzheimer's disease patients have been intensively studied. Numerous experiments have highlighted the involvement of ceramide and monohexosylceramide metabolism in the pathophysiology of the sporadic forms of Parkinson's disease. Moreover, gene mutations of the glucocerebrosidase enzyme were considered as responsible for Parkinson's disease via transition of the monomeric form of α-synuclein to an oligomeric, aggregated toxic form. Disturbances in the metabolism of ceramides were also associated with the appearance of Lewy's bodies. Changes in sphingolipid metabolism were found as a manifestation of Amyotrophic Lateral Sclerosis, both sporadic and family forms, and affected the rate of disease development. Currently, fingolimod (FTY720), a sphingosine-1-phosphate receptor modulator, is the only drug undergoing clinical trials of phase II safety for the treatment of Amyotrophic Lateral Sclerosis. The use of sphingolipids as new diagnostic markers and as targets for innovative therapeutic strategies in different neurodegenerative disorders has been included.

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Section: Sphinganine Sphingosine and Sphingosine-1-phoshatementioning

confidence: 62%

Section: Sphinganine Sphingosine and Sphingosine-1-phoshatementioning

confidence: 99%

Exploring Sphingolipid Implications in Neurodegeneration

Alessenko

Albi

2020

Front. Neurol.

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“…Interestingly, treatment with GM3 slowed the onset of paralysis and increased survival in ASL animal models [ 119 ]. Specifically, in FUS transgenic mice, a model of ASL, a reduction in the S1P/Sph-Spha ratio have been detected in the spinal cord, inducing apoptosis in spinal cord cells [ 120 ]. In addition, there is a large increase in the expression of S1P lyase in motor neurons decreasing the levels of S1P, which has anti-apoptotic properties [ 120 ].…”

Section: Neurodegeneration and Sphingolipid Metabolismmentioning

confidence: 99%

Ceramide/Sphingosine 1-Phosphate Axis as a Key Target for Diagnosis and Treatment in Alzheimer’s Disease and Other Neurodegenerative Diseases

Custodia

Romaus-Sanjurjo

Aramburu-Núñez

et al. 2022

IJMS

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Alzheimer’s disease (AD) is considered the most prevalent neurodegenerative disease and the leading cause of dementia worldwide. Sphingolipids, such as ceramide or sphingosine 1-phosphate, are bioactive molecules implicated in structural and signaling functions. Metabolic dysfunction in the highly conserved pathways to produce sphingolipids may lead to or be a consequence of an underlying disease. Recent studies on transcriptomics and sphingolipidomics have observed alterations in sphingolipid metabolism of both enzymes and metabolites involved in their synthesis in several neurodegenerative diseases, including AD. In this review, we highlight the most relevant findings related to ceramide and neurodegeneration, with a special focus on AD.

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“…Gutner et al demonstrated that, in transgenic mice simulating ALS, the metabolism of Sph, sphinganine and S1P is dysregulated [ 109 ]. In particular, Sph and sphinganine levels were significantly increased mainly in the spinal cord of mice but their levels did not change in brain structures during ALS development.…”

Section: Ceramide and Sphingosine-1-phosphate In Neurodegenerative Di...mentioning

confidence: 99%

Ceramide and Sphingosine-1-Phosphate in Neurodegenerative Disorders and Their Potential Involvement in Therapy

Tringali

Giussani

2022

IJMS

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Neurodegenerative disorders (ND) are progressive diseases of the nervous system, often without resolutive therapy. They are characterized by a progressive impairment and loss of specific brain regions and neuronal populations. Cellular and animal model studies have identified several molecular mechanisms that play an important role in the pathogenesis of ND. Among them are alterations of lipids, in particular sphingolipids, that play a crucial role in neurodegeneration. Overall, during ND, ceramide-dependent pro-apoptotic signalling is promoted, whereas levels of the neuroprotective spingosine-1-phosphate are reduced. Moreover, ND are characterized by alterations of the metabolism of complex sphingolipids. The finding that altered sphingolipid metabolism has a role in ND suggests that its modulation might provide a useful strategy to identify targets for possible therapies. In this review, based on the current literature, we will discuss how bioactive sphingolipids (spingosine-1-phosphate and ceramide) are involved in some ND (Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis) and their possible involvement in therapies.

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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

Cited by 15 publications

References 70 publications

Exploring Sphingolipid Implications in Neurodegeneration

Exploring Sphingolipid Implications in Neurodegeneration

Ceramide/Sphingosine 1-Phosphate Axis as a Key Target for Diagnosis and Treatment in Alzheimer’s Disease and Other Neurodegenerative Diseases

Ceramide and Sphingosine-1-Phosphate in Neurodegenerative Disorders and Their Potential Involvement in Therapy

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