ArticleActa neuropathologica communications2023
Inhibition of acid sphingomyelinase reduces reactive astrocyte secretion of mitotoxic extracellular vesicles and improves Alzheimer's disease pathology in the 5xFAD mouse.
Article in Acta neuropathologica communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 25 citations in OpenAlex.
- RIFT: A Fractal-Holographic Theory of Consciousness and Autopoietic Control.Brain sciences · 2026Article
- Article
- Neuroinflammation in Alzheimer's and Parkinson's diseases: pathogenic mechanisms and therapeutic strategies.Translational neurodegeneration · 2026Review
- Glial cells in chronic inflammation: diversity, dysfunction and therapeutic targeting.Nature reviews. Immunology · 2026Review
- HDL-mimetic peptide treatment reverses APOE4-induced transcriptomic and lipidomic alterations in the brain of humanized APOE mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Glycolysis: The Bridge Between Cellular Interaction and Alzheimer's Disease.Biomolecules · 2026Review
- Ceramide-rich extracellular vesicles as pathogenic biomarkers in traumatic brain injury.bioRxiv : the preprint server for biology · 2026Article
- Sphingolipids in human disease: organ-specific pathologies, chain-length-dependent effects, and translational implications.Journal of translational medicine · 2026Review
- Regulatory mechanisms and research progress of astrocytes in the neuro-endocrine-immune network.Frontiers in human neuroscience · 2026Review
- Complement C1q is associated with neuroinflammation and mediates the association between amyloid-β and tau pathology in Alzheimer's disease.Translational psychiatry · 2025Article
- NEU1-Mediated Extracellular Vesicle Glycosylation in Alzheimer's Disease: Mechanistic Insights into Intercellular Communication and Therapeutic Targeting.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Observational
- Extracellular vesicles: new horizons in neurodegeneration.EBioMedicine · 2025Review
- The roles of extracellular vesicles in mental disorders: information carriers, biomarkers, therapeutic agents.Frontiers in pharmacology · 2025Review
- Evidence that keratinocyte microvesicle particles carrying platelet-activating factor mediate the widespread multiorgan damage associated with intoxicated thermal burn injury.Journal of leukocyte biology · 2024Article
- Extracellular vesicle therapy in neurological disorders.Journal of biomedical science · 2024Review
- Double-Edged Sword: Exploring the Mitochondria-Complement Bidirectional Connection in Cellular Response and Disease.Biology · 2024Review
- Nutritional roles and therapeutic potentials of dietary sphingomyelin in brain diseases.Journal of clinical biochemistry and nutrition · 2024Article
- Extracellular Vesicles in the Central Nervous System: A Novel Mechanism of Neuronal Cell Communication.International journal of molecular sciences · 2024Review
- An efficient and high-throughput method for the evaluation of mitochondrial dysfunction in frozen brain samples after traumatic brain injury.Frontiers in molecular biosciences · 2024Article
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Authors and funding
9 authors at 1 institution in 1 country.
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Abstract
In Alzheimer's disease (AD), reactive astrocytes produce extracellular vesicles (EVs) that affect mitochondria in neurons. Here, we show that Aβ-induced generation of the sphingolipid ceramide by acid sphingomyelinase (A-SMase) triggered proinflammatory cytokine (C1q, TNF-α, IL-1α) release by microglia, which induced the reactive astrocytes phenotype and secretion of EVs enriched with ceramide. These EVs impeded the capacity of neurons to respond to energy demand. Inhibition of A-SMase with Arc39 and Imipramine reduced the secretion of cytokines from microglia, prompting us to test the effect of Imipramine on EV secretion and AD pathology in the 5xFAD mouse model. Brain derived-EVs from 5xFAD mice treated with Imipramine contained reduced levels of the astrocytic marker GFAP, ceramide, and Aβ and did not impair mitochondrial respiration when compared to EVs derived from untreated 5xFAD brain. Consistently, Imipramine-treated 5xFAD mice showed reduced AD pathology. Our study identifies A-SMase inhibitors as potential AD therapy by preventing cyotokine-elicited secretion of mitotoxic EVs from astrocytes.
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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.