ArticleCell death & disease2018
SMPD3 deficiency perturbs neuronal proteostasis and causes progressive cognitive impairment.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
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- Epigenetic and transcriptomic alterations precede amyloidosis in the Alzheimer's disease AppScientific reports · 2025Article
- Neutral sphingomyelinase 2: A promising drug target for CNS disease.Advances in pharmacology (San Diego, Calif.) · 2025Review
- SMPD4-mediated sphingolipid metabolism regulates brain and primary cilia development.Development (Cambridge, England) · 2024Article
- Challenging the conventional wisdom: Re-evaluating Smpd3's role in extracellular vesicle biogenesis.Journal of extracellular biology · 2024Article
- 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
- Proteogenomic network analysis reveals dysregulated mechanisms and potential mediators in Parkinson's disease.Nature communications · 2024Article
- CWAS-Plus: estimating category-wide association of rare noncoding variation from whole-genome sequencing data with cell-type-specific functional data.Briefings in bioinformatics · 2024Article
- SMPD3 expression is spatially regulated in the developing embryo by SOXE factors.Developmental biology · 2024Article
- Exploring the Role of SMPD3 in the lncRNA-miRNA-mRNA Regulatory Network in TBI Progression by Influencing Energy Metabolism.Journal of inflammation research · 2024Article
- Evolving Diagnostic and Treatment Strategies for Pediatric CNS Tumors: The Impact of Lipid Metabolism.Biomedicines · 2023Review
- Discovery of Orally Bioavailable and Brain-Penetrable Prodrugs of the Potent nSMase2 Inhibitor DPTIP.Journal of medicinal chemistry · 2022Article
- Growth Media Conditions Influence the Secretion Route and Release Levels of Engineered Extracellular Vesicles.Advanced healthcare materials · 2022Article
- Neutral sphingomyelinase mediates the co-morbidity trias of alcohol abuse, major depression and bone defects.Molecular psychiatry · 2021Article
- Neonatal stroke enhances interaction of microglia-derived extracellular vesicles with microglial cells.Neurobiology of disease · 2021Article
- The plasma peptides of Alzheimer's disease.Clinical proteomics · 2021Article
- Dual Neutral Sphingomyelinase-2/Acetylcholinesterase Inhibitors for the Treatment of Alzheimer's Disease.ACS chemical biology · 2020Article
- The Golgi Apparatus May Be a Potential Therapeutic Target for Apoptosis-Related Neurological Diseases.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neutral sphingomyelinase smpd3 is most abundantly expressed in neurons of brain. The function of SMPD3 has remained elusive. Here, we report a pathogenetic nexus between absence of SMPD3 in the Golgi compartment (GC) of neurons of the smpd3-/- mouse brain, inhibition of Golgi vesicular protein transport and progressive cognitive impairment. Absence of SMPD3 activity in the Golgi sphingomyelin cycle impedes remodeling of the lipid bilayer, essential for budding and multivesicular body formation. Importantly, we show that inhibition of the Golgi vesicular protein transport causes accumulation of neurotoxic proteins APP, Aβ and phosphorylated Tau, dysproteostasis, unfolded protein response, and apoptosis, which ultimately manifests in progressive cognitive decline, similar to the pathognomonic signatures of familial and sporadic forms of Alzheimer´s disease. This discovery might contribute to the search for other primary pathogenic mechanisms, which link perturbed lipid bilayer structures and protein processing and transport in the neuronal Golgi compartment and neurodegeneration and cognitive deficits.
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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.