ArticleMolecular psychiatry2017
Sphingomyelin-induced inhibition of the plasma membrane calcium ATPase causes neurodegeneration in type A Niemann-Pick disease.
Article in Molecular psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 40 citations in OpenAlex.
- Targeting CD44 reverses sphingomyelin-induced oligodendrocyte maturation arrest in acid sphingomyelinase deficiency.EMBO molecular medicine · 2026Article
- Spectrum and functions of ion channels and transporters in osteoclasts.Bone research · 2026Review
- Egg-derived sphingomyelin induces ferroptosis in cancer cells, depending on intracellular labile iron pool levels.Biochemistry and biophysics reports · 2025Article
- A role for plasma membrane CaPflugers Archiv : European journal of physiology · 2024Article
- Meibomian Gland Shortening Is Associated With Altered Meibum Composition.Investigative ophthalmology & visual science · 2024Article
- Nanoreporter Identifies Lysosomal Storage Disease Lipid Accumulation Intracranially.Nano letters · 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
- Anti-Obesity Effect ofNutrients · 2023Article
- Relationships between ocular surface sphingomyelinases, Meibum and Tear Sphingolipids, and clinical parameters of meibomian gland dysfunction.The ocular surface · 2022Article
- Massive Accumulation of Sphingomyelin Affects the Lysosomal and Mitochondria Compartments and Promotes Apoptosis in Niemann-Pick Disease Type A.Journal of molecular neuroscience : MN · 2022Article
- Impact of Intravenous Trehalose Administration in Patients with Niemann-Pick Disease Types A and B.Journal of clinical medicine · 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
- Genetic defects in the sphingolipid degradation pathway and their effects on microglia in neurodegenerative disease.Cellular signalling · 2021Review
- Contribution of Membrane Lipids to Postsynaptic Protein Organization.Frontiers in synaptic neuroscience · 2021Review
- Inhibition of fatty acid amide hydrolase prevents pathology in neurovisceral acid sphingomyelinase deficiency by rescuing defective endocannabinoid signaling.EMBO molecular medicine · 2020Article
- Unbiased yeast screens identify cellular pathways affected in Niemann-Pick disease type C.Life science alliance · 2020Article
- Adeno-associated viral vector serotype 9-based gene therapy for Niemann-Pick disease type A.Science translational medicine · 2019Article
- Review
- Lipid-induced lysosomal damage after demyelination corrupts microglia protective function in lysosomal storage disorders.The EMBO journal · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Niemann-Pick disease type A (NPA) is a rare lysosomal storage disorder characterized by severe neurological alterations that leads to death in childhood. Loss-of-function mutations in the acid sphingomyelinase (ASM) gene cause NPA, and result in the accumulation of sphingomyelin (SM) in lysosomes and plasma membrane of neurons. Using ASM knockout (ASMko) mice as a NPA disease model, we investigated how high SM levels contribute to neural pathology in NPA. We found high levels of oxidative stress both in neurons from these mice and a NPA patient. Impaired activity of the plasma membrane calcium ATPase (PMCA) increases intracellular calcium. SM induces PMCA decreased activity, which causes oxidative stress. Incubating ASMko-cultured neurons in the histone deacetylase inhibitor, SAHA, restores PMCA activity and calcium homeostasis and, consequently, reduces the increased levels of oxidative stress. No recovery occurs when PMCA activity is pharmacologically impaired or genetically inhibited in vitro. Oral administration of SAHA prevents oxidative stress and neurodegeneration, and improves behavioral performance in ASMko mice. These results demonstrate a critical role for plasma membrane SM in neuronal calcium regulation. Thus, we identify changes in PMCA-triggered calcium homeostasis as an upstream mediator for NPA pathology. These findings can stimulate new approaches for pharmacological remediation in a disease with no current clinical treatments.
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.