ArticleEMBO molecular medicine2014
Pharmacological reversion of sphingomyelin-induced dendritic spine anomalies in a Niemann Pick disease type A mouse model.
Article in EMBO molecular medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- Targeting CD44 reverses sphingomyelin-induced oligodendrocyte maturation arrest in acid sphingomyelinase deficiency.EMBO molecular medicine · 2026Article
- Reelin Increases the Sphingomyelin Content of the Plasma Membrane and Affects the Surface Expression of GPI-Anchored Proteins in Hippocampal Neurons.Journal of neurochemistry · 2025Article
- Stabilizing Immature Dendritic Spines in the Auditory Cortex: A Key Mechanism for mTORC1-Mediated Enhancement of Long-Term Fear Memories.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Nanoreporter Identifies Lysosomal Storage Disease Lipid Accumulation Intracranially.Nano letters · 2023Article
- Immunolocalization of Sphingolipid Catabolism Enzymes along the Nephron: Novel Early Urinary Biomarkers of Renal Damage.International journal of molecular sciences · 2023Article
- Modulation of Dietary Choline Uptake in a Mouse Model of Acid Sphingomyelinase Deficiency.International journal of molecular sciences · 2023Article
- Sphingomyelin 16:0 is a therapeutic target for neuronal death in acid sphingomyelinase deficiency.Cell death & disease · 2023Article
- Association between human blood metabolome and the risk of delirium: a Mendelian Randomization study.Frontiers in endocrinology · 2023Article
- Interactions between the Nicotinic and Endocannabinoid Receptors at the Plasma Membrane.Membranes · 2022Review
- The Neuroprotective Lipocalin Apolipoprotein D Stably Interacts with Specific Subtypes of Detergent-Resistant Membrane Domains in a Basigin-Independent Manner.Molecular neurobiology · 2022Article
- Relationships between ocular surface sphingomyelinases, Meibum and Tear Sphingolipids, and clinical parameters of meibomian gland dysfunction.The ocular surface · 2022Article
- Acid Sphingomyelinase Is a Modulator of Contextual Fear.International journal of molecular sciences · 2022Article
- c-Abl Activation Linked to Autophagy-Lysosomal Dysfunction Contributes to Neurological Impairment in Niemann-Pick Type A Disease.Frontiers in cell and developmental biology · 2022Article
- Nanoscale Sub-Compartmentalization of the Dendritic Spine Compartment.Biomolecules · 2021Review
- The Multiple Roles of Sphingomyelin in Parkinson's Disease.Biomolecules · 2021Review
- Article
- Inhibition of fatty acid amide hydrolase prevents pathology in neurovisceral acid sphingomyelinase deficiency by rescuing defective endocannabinoid signaling.EMBO molecular medicine · 2020Article
- Cellular Membranes, a Versatile Adaptive Composite Material.Frontiers in cell and developmental biology · 2020Review
- Pre-clinical Mouse Models of Neurodegenerative Lysosomal Storage Diseases.Frontiers in molecular biosciences · 2020Review
- Adeno-associated viral vector serotype 9-based gene therapy for Niemann-Pick disease type A.Science translational medicine · 2019Article
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Authors and funding
8 authors at 5 institutions in 4 countries.
Funding
Abstract
Understanding the role of lipids in synapses and the aberrant molecular mechanisms causing the cognitive deficits that characterize most lipidosis is necessary to develop therapies for these diseases. Here we describe sphingomyelin (SM) as a key modulator of the dendritic spine actin cytoskeleton. We show that increased SM levels in neurons of acid sphingomyelinase knock out mice (ASMko), which mimic Niemann Pick disease type A (NPA), result in reduced spine number and size and low levels of filamentous actin. Mechanistically, SM accumulation decreases the levels of metabotropic glutamate receptors type I (mGluR1/5) at the synaptic membrane impairing membrane attachment and activity of RhoA and its effectors ROCK and ProfilinIIa. Pharmacological enhancement of the neutral sphingomyelinase rescues the aberrant molecular and morphological phenotypes in vitro and in vivo and improves motor and memory deficits in ASMko mice. Altogether, these data demonstrate the influence of SM and its catabolic enzymes in dendritic spine physiology and contribute to our understanding of the cognitive deficits of NPA patients, opening new perspectives for therapeutic interventions.
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