ArticleScientific reports2015
Cytoplasmic sphingosine-1-phosphate pathway modulates neuronal autophagy.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Differential Ceramide Metabolism in Autogenous and Reactive Obsessions: A Biomarker Perspective in OCD.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2026Article
- Sphingosine kinase 2 regulates protein ubiquitination networks in neurons.Molecular and cellular neurosciences · 2024Article
- The role of sphingosine-1-phosphate in autophagy and related disorders.Cell death discovery · 2023Review
- The Tardigrade damage suppressor protein Dsup promotes DNA damage in neurons.Molecular and cellular neurosciences · 2023Article
- The SphK1/S1P Axis Regulates Synaptic Vesicle Endocytosis via TRPC5 Channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- 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
- Acid sphingomyelinase/ceramide system in schizophrenia: implications for therapeutic intervention as a potential novel target.Translational psychiatry · 2022Review
- Deletion of SUMO1 attenuates behavioral and anatomical deficits by regulating autophagic activities in Huntington disease.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Early Life Stress and Metabolic Plasticity of Brain Cells: Impact on Neurogenesis and Angiogenesis.Biomedicines · 2021Review
- Article
- Role of sphingolipid metabolism in neurodegeneration.Journal of neurochemistry · 2021Review
- Article
- Mutant Huntingtin stalls ribosomes and represses protein synthesis in a cellular model of Huntington disease.Nature communications · 2021Article
- A Rationale for Hypoxic and Chemical Conditioning in Huntington's Disease.International journal of molecular sciences · 2021Review
- The ubiquitin ligase UBE4B regulates amyloid precursor protein ubiquitination, endosomal trafficking, and amyloid β42 generation and secretion.Molecular and cellular neurosciences · 2020Article
- Precision Calcium Imaging of Dense Neural Populations via a Cell-Body-Targeted Calcium Indicator.Neuron · 2020Article
- Bioenergetic deficits in Huntington's disease iPSC-derived neural cells and rescue with glycolytic metabolites.Human molecular genetics · 2020Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Autophagy is an important homeostatic mechanism that eliminates long-lived proteins, protein aggregates and damaged organelles. Its dysregulation is involved in many neurodegenerative disorders. Autophagy is therefore a promising target for blunting neurodegeneration. We searched for novel autophagic pathways in primary neurons and identified the cytosolic sphingosine-1-phosphate (S1P) pathway as a regulator of neuronal autophagy. S1P, a bioactive lipid generated by sphingosine kinase 1 (SK1) in the cytoplasm, is implicated in cell survival. We found that SK1 enhances flux through autophagy and that S1P-metabolizing enzymes decrease this flux. When autophagy is stimulated, SK1 relocalizes to endosomes/autophagosomes in neurons. Expression of a dominant-negative form of SK1 inhibits autophagosome synthesis. In a neuron model of Huntington's disease, pharmacologically inhibiting S1P-lyase protected neurons from mutant huntingtin-induced neurotoxicity. These results identify the S1P pathway as a novel regulator of neuronal autophagy and provide a new target for developing therapies for neurodegenerative disorders.
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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.