ArticleCell death and differentiation2011
Sphingosine-1-phosphate links glycosphingolipid metabolism to neurodegeneration via a calpain-mediated mechanism.
Article in Cell death and differentiation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 81 citations in OpenAlex.
- The physiological and pathological effects of sphingolipid metabolism and signaling in the central nervous system.Brain pathology (Zurich, Switzerland) · 2026Review
- A disproportionality analysis of nervous system adverse events associated with disease-modifying therapies in multiple sclerosis: insights from the FDA adverse event reporting system (FAERS).Journal of neurology · 2025Article
- Sphingosine phosphate lyase insufficiency syndrome as a primary immunodeficiency state.Advances in biological regulation · 2024Review
- Sphingosine 1-Phosphate Lyase in the Developing and Injured Nervous System: a Dichotomy?Molecular neurobiology · 2023Review
- Article
- Recent Insight into the Role of Sphingosine-1-Phosphate Lyase in Neurodegeneration.International journal of molecular sciences · 2023Review
- S1P Released by SGPL1-Deficient Astrocytes Enhances Astrocytic ATP Production via S1PRInternational journal of molecular sciences · 2023Article
- Treatment with THI, an inhibitor of sphingosine-1-phosphate lyase, modulates glycosphingolipid metabolism and results therapeutically effective in experimental models of Huntington's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Sphingosine 1-Phoshpate Receptors are Located in Synapses and Control Spontaneous Activity of Mouse Neurons in Culture.Neurochemical research · 2022Article
- Uncovering the 'sphinx' of sphingosine 1-phosphate signalling: from cellular events to organ morphogenesis.Biological reviews of the Cambridge Philosophical Society · 2022Review
- To Be or Not to Be: The Divergent Action and Metabolism of Sphingosine-1 Phosphate in Pancreatic Beta-Cells in Response to Cytokines and Fatty Acids.International journal of molecular sciences · 2022Review
- Neurological Consequences of Sphingosine Phosphate Lyase Insufficiency.Frontiers in cellular neuroscience · 2022Review
- Sphingolipid metabolism governs Purkinje cell patterned degeneration inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Genotype/Phenotype Interactions and First Steps Toward Targeted Therapy for Sphingosine Phosphate Lyase Insufficiency Syndrome.Cell biochemistry and biophysics · 2021Review
- Role of sphingolipid metabolism in neurodegeneration.Journal of neurochemistry · 2021Review
- MRI Spectrum of Brain Involvement in Sphingosine-1-Phosphate Lyase Insufficiency Syndrome.AJNR. American journal of neuroradiology · 2020Article
- Positron Emission Tomography in the Inflamed Cerebellum: Addressing Novel Targets among G Protein-Coupled Receptors and Immune Receptors.Pharmaceutics · 2020Review
- Article
- Review
- Sphingosine-1-Phosphate: Its Pharmacological Regulation and the Treatment of Multiple Sclerosis: A Review Article.Biomedicines · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have recently reported that the bioactive lipid sphingosine-1-phosphate (S1P), usually signaling proliferation and anti-apoptosis induces neuronal death when generated by sphingosine-kinase2 and when accumulation due to S1P-lyase deficiency occurs. In the present study, we identify the signaling cascade involved in the neurotoxic effect of sphingoid-base phosphates. We demonstrate that the calcium-dependent cysteine protease calpain mediates neurotoxicity by induction of the endoplasmic reticulum stress-specific caspase cascade and activation of cyclin-dependent kinase5 (CDK5). The latter is involved in an abortive reactivation of the cell cycle and also enhances tau phosphorylation. Neuroanatomical studies in the cerebellum document for the first time that indeed neurons with abundant S1P-lyase expression are those, which degenerate first in S1P-lyase-deficient mice. We therefore propose that an impaired metabolism of glycosphingolipids, which are prevalent in the central nervous system, might be linked via S1P, their common catabolic intermediate, to neuronal death.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.