ArticleThe American journal of pathology2011
Endosomal/lysosomal processing of gangliosides affects neuronal cholesterol sequestration in Niemann-Pick disease type C.
Article in The American journal of pathology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Mass spectrometry-based lipid analysis in NPC1 disease: Methods for phosphoinositide quantification, lipid imaging, and myelin lipid profiling.Methods in enzymology · 2026Article
- Deficiency of Toll-like receptor 2 is a driver of sex-related compositional and structural rearrangements of membrane lipids.Communications chemistry · 2025Article
- Fighting fire with fire: PLA2G15 inhibition mobilizes BMP lipids to combat NPC1 disease.Metabolism open · 2025Article
- Biomarker Validation in NPC1: Foundations for Clinical Trials and Regulatory Alignment.Journal of inherited metabolic disease · 2025Review
- Advances in mass spectrometry of lipids for the investigation of Niemann-pick type C disease.Lipids in health and disease · 2025Review
- Endothelial and neuronal engagement by AAV-BR1 gene therapy alleviates neurological symptoms and lipid deposition in a mouse model of Niemann-Pick type C2.Fluids and barriers of the CNS · 2025Article
- Pathogenesis of Alzheimer's disease: Involvement of the choroid plexus.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Biochemical Correction of GM2 Ganglioside Accumulation in AB-Variant GM2 Gangliosidosis.International journal of molecular sciences · 2023Article
- The Antifungal Antibiotic Filipin as a Diagnostic Tool of Cholesterol Alterations in Lysosomal Storage Diseases and Neurodegenerative Disorders.Antibiotics (Basel, Switzerland) · 2023Review
- A major role for adenosine APurinergic signalling · 2022Article
- Differential involvement of hippocampal subfields in Niemann-Pick type C disease: a case-control study.Metabolic brain disease · 2021Article
- Mass spectrometry imaging and LC/MS reveal decreased cerebellar phosphoinositides in Niemann-Pick type C1-null mice.Journal of lipid research · 2020Article
- Mechanism of Secondary Ganglioside and Lipid Accumulation in Lysosomal Disease.International journal of molecular sciences · 2020Review
- NPC1 enables cholesterol mobilization during long-term potentiation that can be restored in Niemann-Pick disease type C by CYP46A1 activation.EMBO reports · 2019Article
- 2-Hydroxypropyl-β-cyclodextrin is the active component in a triple combination formulation for treatment of Niemann-Pick C1 disease.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2019Article
- Hepatic pathology and altered gene transcription in a murine model of acid ceramidase deficiency.Laboratory investigation; a journal of technical methods and pathology · 2019Article
- Mass spectrometry imaging of lipids: untargeted consensus spectra reveal spatial distributions in Niemann-Pick disease type C1.Journal of lipid research · 2018Article
- The Extending Spectrum of NPC1-Related Human Disorders: From Niemann-Pick C1 Disease to Obesity.Endocrine reviews · 2018Review
- Targeted deletion of GD3 synthase protects against MPTP-induced neurodegeneration.Genes, brain, and behavior · 2017Article
- Engineering Botulinum Neurotoxin C1 as a Molecular Vehicle for Intra-Neuronal Drug Delivery.Scientific reports · 2017Article
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7 authors.
Funding
Abstract
Niemann-Pick disease type C (NPC) is a severe neurovisceral lysosomal storage disorder caused by defects in NPC1 or NPC2 proteins. Although numerous studies support the primacy of cholesterol storage, neurons of double-mutant mice lacking both NPC1 and an enzyme required for synthesis of all complex gangliosides (β1,4GalNAc transferase) have been reported to exhibit dramatically reduced cholesterol sequestration. Here we show that NPC2-deficient mice lacking this enzyme also exhibit reduced cholesterol, but that genetically restricting synthesis to only a-series gangliosides fully restores neuronal cholesterol storage to typical disease levels. Examining the subcellular locations of sequestered compounds in neurons lacking NPC1 or NPC2 by confocal microscopy revealed that cholesterol and the two principal storage gangliosides (GM2 and GM3) were not consistently co-localized within the same intracellular vesicles. To determine whether the lack of GM2 and GM3 co-localization was due to differences in synthetic versus degradative pathway expression, we generated mice lacking both NPC1 and lysosomal β-galactosidase, and therefore unable to generate GM2 and GM3 in lysosomes. Double mutants lacked both gangliosides, indicating that each is the product of endosomal/lysosomal processing. Unexpectedly, GM1 accumulation in double mutants increased compared to single mutants consistent with a direct role for NPC1 in ganglioside salvage. These studies provide further evidence that NPC1 and NPC2 proteins participate in endosomal/lysosomal processing of both sphingolipids and cholesterol.
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