ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Fibrillar amyloid-beta-activated human astroglia kill primary human neurons via neutral sphingomyelinase: implications for Alzheimer's disease.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 129 citations in OpenAlex.
- Development of a FRET-Based Assay for Human Neutral Sphingomyelinase 2.Biochemistry · 2026Article
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- Prospect of Muscle-Building Supplement HMB in Alzheimer's Disease.Journal of clinical & experimental immunology · 2026Article
- The novel sphingolipids cP1P and P1P attenuate neuroinflammation and enhance S1PR1/Akt/mTOR signaling to mitigate cognitive decline in an Alzheimer's disease mouse model.Cell communication and signaling : CCS · 2025Article
- Neurotoxic amyloid β-peptide and tau produce cytokine-like effects on PMCA in glioblastoma cell lines, enhancing its activity and isoforms expression.FEBS open bio · 2025Article
- A human neuron alzheimer's disease model reveals barriers to senolytic translatability.Alzheimer's research & therapy · 2025Article
- Streamlined Full-Length Total RNA Sequencing of Paraformaldehyde-Fixed Brain Tissues.International journal of molecular sciences · 2024Article
- Synthesis of Fluorophore Based Functional Material for Selective Detection of AlJournal of fluorescence · 2023Review
- Tau fibrils induce glial inflammation and neuropathology via TLR2 in Alzheimer's disease-related mouse models.The Journal of clinical investigation · 2023Article
- Proteomics of the astrocyte secretome reveals changes in their response to soluble oligomeric Aβ.Journal of neurochemistry · 2023Article
- The relationship among amyloid-β deposition, sphingomyelin level, and the expression and function of P-glycoprotein in Alzheimer's disease pathological process.Neural regeneration research · 2023Article
- Cinnamein Inhibits the Induction of Nitric Oxide and Proinflammatory Cytokines in Macrophages, Microglia and Astrocytes.Journal of clinical & experimental immunology · 2023Article
- Sphingomyelinases in retinas and optic nerve heads: Effects of ocular hypertension and ischemia.Experimental eye research · 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
- Treadmill exercise reduces α-synuclein spreading via PPARα.Cell reports · 2022Article
- Mechanistic Insights into Selective Autophagy Subtypes in Alzheimer's Disease.International journal of molecular sciences · 2022Review
- Protective Effect of Low Dose of Methamphetamine on The Amount of Extracellular Glutamine in Primary Fetal Human Astrocytes Induced by Amyloid Beta.Cell journal · 2022Article
- Article
- Ceramide Metabolism and Parkinson's Disease-Therapeutic Targets.Biomolecules · 2021Review
- Selective autophagy as a therapeutic target for neurological diseases.Cellular and molecular life sciences : CMLS · 2021Review
25 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Glial activation plays an important role in the pathogenesis of various neurodegenerative disorders including Alzheimer's disease. However, molecular mechanisms by which activated glia could kill neurons are poorly understood. The present study underlines the importance of neutral sphingomyelinase (N-SMase) in mediating the damaging effect of fibrillar amyloid-β 1-42 (Aβ1-42) peptide-activated astroglia on neurons. In transwell experiments, soluble products released from activated primary human astroglia induced the activation of neutral sphingomyelinase (N-SMase), production of ceramide, and cell death in primary human neurons. Protection of neurons from cytotoxic effects of activated astroglia by antisense knockdown of N-SMase, but not acidic sphingomyelinase (A-SMase), suggests that soluble products released from activated astroglia kill neurons via N-SMase but not A-SMase. Next we examined the role of N-SMase in the activation of human astroglia. Interestingly, knockdown of N-SMase, but not A-SMase, by either antisense oligonucleotides or chemical inhibitor, prevented the induction of proinflammatory molecules [tumor necrosis factor-α, inducible nitric oxide synthase, interleukin-1β (IL-1β), and IL-6] and the activation of nuclear factor-κB in Aβ1-42-activated astroglia. Subsequently, fibrillar Aβ peptides also induced the activation of N-SMase and ceramide in vivo in mouse cortex. Most importantly, antisense knockdown of N-SMase, but not A-SMase, decreased the activation of astroglia and protected neurons from fibrillar Aβ toxicity in vivo in the cortex. Together, it is apparent that both the activation of astroglia by Aβ and that the cytotoxicity of activated astroglia on neurons depend on N-SMase.
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