ArticleFrontiers in molecular neuroscience2019
Inhibition of nSMase2 Reduces the Transfer of Oligomeric α-Synuclein Irrespective of Hypoxia.
Article in Frontiers in molecular neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- Exosome Biology at the Interface of Neurodegeneration and Therapeutic Innovation.Molecular neurobiology · 2026Review
- Small Extracellular Vesicles from Neural Cells: Physiological and Pathological Roles, and Potential in Neurodegenerative Therapy.Advanced healthcare materials · 2026Review
- Lipid Messengers: Mechanisms and Clinical Applications of Exosomal Lipids in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Multi-omic analysis reveals lipid dysregulation associated with mitochondrial dysfunction in parkinson's disease brain.Nature communications · 2025Article
- Molecular Mechanisms of Extracellular Vesicle Biogenesis and Their Impact on the Design of Custom EVs.Advanced healthcare materials · 2025Review
- Double-Negative CD4 CD8 Absolute Count Plays a Mediating Role in the Causal Relationship Between Plasma Lipids and Parkinson's Disease: A Mendel Randomized Study.Molecular neurobiology · 2025Article
- Investigating plasma lipid profiles in association with Parkinson's disease risk.NPJ Parkinson's disease · 2025Review
- Neutral sphingomyelinase 2: A promising drug target for CNS disease.Advances in pharmacology (San Diego, Calif.) · 2025Review
- ESCRT disruption provides evidence against trans-synaptic signaling via extracellular vesicles.The Journal of cell biology · 2024Article
- Exosomes: A Cellular Communication Medium That Has Multiple Effects On Brain Diseases.Molecular neurobiology · 2024Review
- Extracellular Vesicle Inhibitors Enhance Cholix-Induced Cell Death via Regulation of the JNK-Dependent Pathway.Toxins · 2024Article
- Article
- Transcriptomics analysis reveals potential regulatory role of nSMase2 (Smpd3) in nervous system development and function of middle-aged mouse brains.Genes, brain, and behavior · 2024Article
- ESCRT disruption provides evidence against transsynaptic signaling functions for extracellular vesicles.bioRxiv : the preprint server for biology · 2024Article
- Extracellular high molecular weight α-synuclein oligomers induce cell death by disrupting the plasma membrane.NPJ Parkinson's disease · 2023Article
- Review
- Extracellular vesicles in β cell biology: Role of lipids in vesicle biogenesis, cargo, and intercellular signaling.Molecular metabolism · 2022Review
- Article
- Involvement of Ceramide Metabolism in Cerebral Ischemia.Frontiers in molecular biosciences · 2022Review
- The Multiple Roles of Sphingomyelin in Parkinson's Disease.Biomolecules · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, extracellular vesicles (EVs), such as exosomes, have been proposed to play an influential role in the cell-to-cell spread of neurodegenerative diseases, including the intercellular transmission of α-synuclein (α-syn). However, the regulation of EV biogenesis and its relation to Parkinson's disease (PD) is only partially understood. The generation of EVs through the ESCRT-independent pathway depends on the hydrolysis of sphingomyelin by neutral sphingomyelinase 2 (nSMase2) to produce ceramide, which causes the membrane of endosomal multivesicular bodies to bud inward. nSMase2 is sensitive to oxidative stress, a common process in PD brains; however, little is known about the role of sphingomyelin metabolism in the pathogenesis of PD. This is the first study to show that inhibiting nSMase2 decreases the transfer of oligomeric aggregates of α-syn between neuron-like cells. Furthermore, it reduced the accumulation and aggregation of high-molecular-weight α-syn. Hypoxia, as a model of oxidative stress, reduced the levels of nSMase2, but not its enzymatic activity, and significantly altered the lipid composition of cells without affecting EV abundance or the transfer of α-syn. These data show that altering sphingolipids can mitigate the spread of α-syn, even under hypoxic conditions, potentially suppressing PD progression.
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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.