ArticleGlia2019
Lipid transporter Spns2 promotes microglia pro-inflammatory activation in response to amyloid-beta peptide.
Article in Glia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 49 citations in OpenAlex.
- A Novel Reporter Mouse for Astrocyte-Derived Extracellular Vesicles Reveals Enrichment of Cargo at Neuronal Mitochondria.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Neuroinflammation in Alzheimer's and Parkinson's diseases: pathogenic mechanisms and therapeutic strategies.Translational neurodegeneration · 2026Review
- A novel reporter mouse for astrocyte-derived extracellular vesicles reveals trafficking of cargo to neuronal mitochondria.bioRxiv : the preprint server for biology · 2026Article
- Sphingolipid-Neuroinflammation Axis in Parkinson's Disease: Focus on S1P/SPHK1-NF‑κB Signaling.Journal of inflammation research · 2026Review
- Assessment of Spinster homologue 2 (Spns2)-dependent transport of sphingosine-1-phosphate as a therapeutic target.British journal of pharmacology · 2025Article
- Stress Accelerates Depressive-Like Behavior through Increase of SPNS2 Expression in Tg2576 Mice.Biomolecules & therapeutics · 2025Article
- Lipid-nanoparticle-induced vacuolization in microglia.Communications biology · 2024Article
- The neuron-specific IIS/FOXO transcriptome in aged animals reveals regulatory mechanisms of cognitive aging.eLife · 2024Article
- Sphingosine-1-phosphate Signalling in Aneurysmal Subarachnoid Haemorrhage: Basic Science to Clinical Translation.Translational stroke research · 2024Review
- Cortical lipid metabolic pathway alteration of early Alzheimer's disease and candidate drugs screen.European journal of medical research · 2024Article
- Gut microbiota metabolites: potential therapeutic targets for Alzheimer's disease?Frontiers in pharmacology · 2024Review
- Repurposing drugs against Alzheimer's disease: can the anti-multiple sclerosis drug fingolimod (FTY720) effectively tackle inflammation processes in AD?Journal of neural transmission (Vienna, Austria : 1996) · 2023Review
- Functional roles of sphingolipids in immunity and their implication in disease.Experimental & molecular medicine · 2023Review
- The Implications of Microglial Regulation in Neuroplasticity-Dependent Stroke Recovery.Biomolecules · 2023Review
- New insights into hypothalamic neurogenesis disruption after acute and intense stress: implications for microglia and inflammation.Frontiers in neuroscience · 2023Article
- Propofol inhibits neuroinflammation and metabolic reprogramming in microgliaFrontiers in pharmacology · 2023Article
- p38 MAPK Is a Major Regulator of Amyloid Beta-Induced IL-6 Expression in Human Microglia.Molecular neurobiology · 2022Article
- Sphingosine 1-phosphate signaling in perivascular cells enhances inflammation and fibrosis in the kidney.Science translational medicine · 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
- Neutral Sphingomyelinase 2 Mediates Oxidative Stress Effects on Astrocyte Senescence and Synaptic Plasticity Transcripts.Molecular neurobiology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Accumulating evidence indicates that neuroinflammation contributes to the pathogenesis and exacerbation of neurodegenerative disorders, such as Alzheimer's disease (AD). Sphingosine-1-phosphate (S1P) is a pleiotropic bioactive lipid that regulates many pathophysiological processes including inflammation. We present evidence here that the spinster homolog 2 (Spns2), a S1P transporter, promotes microglia pro-inflammatory activation in vitro and in vivo. Spns2 knockout (Spns2KO) in primary cultured microglia resulted in significantly reduced levels of pro-inflammatory cytokines induced by lipopolysaccharide (LPS) and amyloid-beta peptide 1-42 oligomers (Aβ42) when compared with littermate controls. Fingolimod (FTY720), a S1P receptor 1 (S1PR1) functional antagonist and FDA approved drug for relapsing-remitting multiple sclerosis, partially blunted Aβ42-induced pro-inflammatory cytokine generation, suggesting that Spns2 promotes microglia pro-inflammatory activation through S1P-signaling. Spns2KO significantly reduced Aβ42-induced nuclear factor kappa B (NFκB) activity. S1P increased, while FTY720 dampened, Aβ42-induced NFκB activity, suggesting that Spns2 activates microglia inflammation through, at least partially, NFκB pathway. Spns2KO mouse brains showed significantly reduced Aβ42-induced microglia activation/accumulation and reduced levels of pro-inflammatory cytokines when compared with age-matched controls. More interestingly, Spns2KO ameliorated Aβ42-induced working memory deficit detected by Y-Maze. In summary, these results suggest that Spns2 promotes pro-inflammatory polarization of microglia and may play a crucial role in AD pathogenesis.
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.