ArticleMolecular neurobiology2014
Ceramide in the molecular mechanisms of neuronal cell death. The role of sphingosine-1-phosphate.
Article in Molecular neurobiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Tea tree oil, a vibrant source of neuroprotection via neuroinflammation inhibition: a critical insight into repurposingJournal of Zhejiang University. Science. B · 2023Pooled it
- Multitarget Actions of Pentacyclic Triterpenic Acids in Alzheimer's Disease: Mechanistic Insights.Molecules (Basel, Switzerland) · 2026Review
- Circulating Sphingomyelins Correlate With Plasma T-Tau in Cognitively Unimpaired Older Adults at Risk of Developing Alzheimer's Disease.Journal of neurochemistry · 2026Article
- Ceramide-rich extracellular vesicles as pathogenic biomarkers in traumatic brain injury.bioRxiv : the preprint server for biology · 2026Article
- Molecular mechanisms of exercise-induced improvements in Alzheimer's disease: a focus on lipid homeostasis.Translational neurodegeneration · 2026Review
- A Lipid Road to Neuroimmunology: Fatty Acids Linking Immune and Nervous Systems.Neuroimmunomodulation · 2026Review
- Ferroptosis-immune crosstalk in ionizing radiation-induced testicular injury: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
- The Associations of Circulating Sphingolipid Levels with Future Loss of Vibration and Light Pressure Sensation in the Lower Limb.Biomedicines · 2025Article
- Multiomics analysis unveils an inosine-sensitive DNA damage response in neurogenic bladder after spinal cord injury.JCI insight · 2025Article
- Ceramide as a Promising Tool for Diagnosis and Treatment of Clinical Diseases: A Review of Recent Advances.Metabolites · 2025Review
- 4-Hydroxynonenal from Mitochondrial and Dietary Sources Causes Lysosomal Cell Death for Lifestyle-Related Diseases.Nutrients · 2024Review
- Protective Role of Sphingosine-1-Phosphate During Radiation-Induced Testicular Injury.Antioxidants (Basel, Switzerland) · 2024Review
- Modulation of Ceramide-Induced Apoptosis in Enteric Neurons by Aryl Hydrocarbon Receptor Signaling: Unveiling a New Pathway beyond ER Stress.International journal of molecular sciences · 2024Article
- Assessment of the level of apoptosis in differentiated pseudo-neuronal cells derived from neural stem cells under the influence of various inducers.American journal of stem cells · 2024Review
- The Biomarkers in Extreme Longevity: Insights Gained from Metabolomics and Proteomics.International journal of medical sciences · 2024Review
- Sphingolipids in Cerebrospinal Fluid and Plasma Lipoproteins ofJournal of Alzheimer's disease reports · 2023Article
- Functional consequences of brain exposure to saturated fatty acids: From energy metabolism and insulin resistance to neuronal damage.Endocrinology, diabetes & metabolism · 2023Review
- Dihydroceramide desaturase 1 (DES1) promotes anchorage-independent survival downstream of HER2-driven glucose uptake and metabolism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Ceramide/Sphingosine 1-Phosphate Axis as a Key Target for Diagnosis and Treatment in Alzheimer's Disease and Other Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- Compartmentalization of Sphingolipid metabolism: Implications for signaling and therapy.Pharmacology & therapeutics · 2022Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ceramide and sphingosine-1-phosphate (S1P), two important bioactive sphingolipids, have been suggested as being key players in the pathology of Alzheimer's disease in inflammation and cancer. However, their role in the molecular mechanisms of neuronal death has not been fully elucidated. Our study indicated that ceramide significantly enhanced the level of free radicals and decreased the viability of the human neuroblastoma cell line (SH-SY5Y) through inhibition of the prosurvival PI3-K/Akt pathway. Ceramide also decreased anti-apoptotic (Bcl-2) and increased pro-apoptotic (Bax, Hrk) mRNA/protein levels. Concomitantly, our study indicated that ceramide induced poly(ADP-ribose) polymerase-1 (PARP-1) activation and accumulation of poly(ADP-ribose) PAR, a signalling molecule involved in mitochondria-nucleus cross-talk and mitochondria integrity. Ceramide treatment significantly decreased the level of apoptosis-inducing factor (AIF) in the mitochondria. The PARP-1 inhibitor (PJ-34) prevented AIF release from the mitochondria. In addition, our data showed that exogenously added S1P increased the viability of SH-SY5Y through the S1P (1,3) receptor-dependent mechanism. It was also revealed that the S1P and PARP-1 inhibitor (PJ-34) decreased oxidative stress, gene expression of the pro-apoptotic Hrk protein and up-regulated the anti-apoptotic Bcl-2 protein. Our data demonstrate that neuronal cell death evoked by ceramide is regulated by PARP/PAR/AIF and by S1P receptor signalling. In summary, our results suggest that PARP-1 inhibitor(s) and modulators of sphingosine-1-phosphate receptor(s) should be considered in potential therapeutic strategies directed at neurodegenerative diseases.
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Registered trials
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