ArticleMolecular neurobiology2020
Fingolimod Affects Transcription of Genes Encoding Enzymes of Ceramide Metabolism in Animal Model of Alzheimer's Disease.
Article in Molecular neurobiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Fat on Fire: Disrupted Microglial Lipid Metabolism as a Driver of Anesthetic Neurotoxicity.Neuroscience bulletin · 2026Review
- Circular RNAEnvironment & health (Washington, D.C.) · 2026Article
- The Role of Sphingosine-1-Phosphate Signaling in Cerebral Ischemia/Reperfusion Injury and Alzheimer's Disease Pathology.International journal of molecular sciences · 2026Review
- Correlation Between Gut Microbiota and Plasma Metabolites in a Mouse Model for Post-Traumatic Stress Disorder.Metabolites · 2026Article
- Ceramide synthase 4 interferes with replication of influenza virus but is downregulated by infection.Journal of virology · 2025Article
- Regulation of presynaptic homeostatic plasticity by glial signalling in Alzheimer's disease.The Journal of physiology · 2025Review
- The sphingosine-1-phosphate signaling pathway (sphingosine-1-phosphate and its receptor, sphingosine kinase) and epilepsy.Epilepsia open · 2025Review
- Therapeutic Potential of Fingolimod on Psychological Symptoms and Cognitive Function in Neuropsychiatric and Neurological Disorders.Neurochemical research · 2024Review
- Metabolomics of Multiple Sclerosis Lesions Demonstrates Lipid Changes Linked to Alterations in Transcriptomics-Based Cellular Profiles.Neurology(R) neuroimmunology & neuroinflammation · 2024Article
- Lipid metabolism-related genes are involved in the occurrence of asthma and regulate the immune microenvironment.BMC genomics · 2024Article
- Therapeutic implications for sphingolipid metabolism in metabolic dysfunction-associated steatohepatitis.Frontiers in endocrinology · 2024Review
- The Effect of FTY720 on Sphingolipid Imbalance and Cognitive Decline in Aged EFAD Mice.Journal of Alzheimer's disease reports · 2024Article
- Unique Bioactives from Zombie Fungus (Nutrients · 2023Review
- Fingolimod Modulates the Gene Expression of Proteins Engaged in Inflammation and Amyloid-Beta Metabolism and Improves Exploratory and Anxiety-Like Behavior in Obese Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- Fingolimod protects against neurovascular unit injury in a rat model of focal cerebral ischemia/reperfusion injury.Neural regeneration research · 2023Article
- Fingolimod effects on the brain are mediated through biochemical modulation of bioenergetics, autophagy, and neuroinflammatory networks.Proteomics · 2022Article
- Molecular Pharmacology and Novel Potential Therapeutic Applications of Fingolimod.Frontiers in pharmacology · 2022Review
- High-Quality Nursing Combined with the Whole-Course Responsibility Nursing Intervention Reduces the Incidence of Complications in Severe Aneurysmal Subarachnoid Hemorrhage.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Modulation of the gut microbiota and lipidomic profiles by black chokeberry (Frontiers in nutrition · 2022Article
- Sphingolipids as Regulators of Neuro-Inflammation and NADPH Oxidase 2.Neuromolecular medicine · 2021Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The imbalance in sphingolipid signaling may be critically linked to the upstream events in the neurodegenerative cascade of Alzheimer's disease (AD). We analyzed the influence of mutant (V717I) amyloid β precursor protein (AβPP) transgene on sphingolipid metabolism enzymes in mouse hippocampus. At 3 months of age AβPP/Aβ presence upregulated enzymes of ceramide turnover on the salvage pathway: ceramide synthases (CERS2, CERS4, CERS6) and also ceramidase ACER3. At 6 months, only CERS6 was elevated, and no ceramide synthase was increased at 12 months. However, sphingomyelin synthases, which utilize ceramide on the sphingomyelinase pathway, were reduced (SGMS1 at 12 and SGMS2 at 6 months). mRNAs for sphingomyelin synthases SGMS1 and SGMS2 were also significantly downregulated in human AD hippocampus and neocortex when compared with age-matched controls. Our findings suggest early-phase deregulation of sphingolipid homeostasis in favor of ceramide signaling. Fingolimod (FTY720), a modulator of sphingosine-1-phosphate receptors countered the AβPP-dependent upregulation of hippocampal ceramide synthase CERS2 at 3 months. Moreover, at 12 months, FTY720 increased enzymes of ceramide-sphingosine turnover: CERS4, ASAH1, and ACER3. We also observed influence of fingolimod on the expression of the sphingomyelinase pathway enzymes. FTY720 counteracted the AβPP-linked reduction of sphingomyelin synthases SGMS1/2 (at 12 and 6 months, respectively) and led to elevation of sphingomyelinase SMPD2 (at 6 and 12 months). Therefore, our results demonstrate potentially beneficial, age-specific effects of fingolimod on transcription of sphingolipid metabolism enzymes in an animal model of AD.
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