ArticleCell death & disease2016
Necroptosis in Niemann-Pick disease, type C1: a potential therapeutic target.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Receptor-interacting protein kinase 1 (RIPK1) as a therapeutic target.Nature reviews. Drug discovery · 2020Pooled it
- Safety, pharmacokinetics and target engagement of novel RIPK1 inhibitor SAR443060 (DNL747) for neurodegenerative disorders: Randomized, placebo-controlled, double-blind phase I/Ib studies in healthy subjects and patients.Clinical and translational science · 2022Trial
- Lack of cathepsin B increases severity in Niemann-Pick disease, type C1 mice.Neuroscience letters · 2026Article
- NPC1 deficiency engages a lysosome-genome-immune program linked to neurodegeneration and cellular aging signatures.bioRxiv : the preprint server for biology · 2026Article
- Probing Allosteric Kinase Modulators as Next Game-Changers in Fighting Neurodegeneration.Journal of medicinal chemistry · 2026Review
- From autophagy-lysosomal deficits to neurodegeneration in Niemann-Pick type C1 disease: implications for age-related neurodegenerative disorders.Frontiers in neuroscience · 2026Review
- Upregulation of Receptor Interacting Protein 1 Induced by UVB Contributes to Photodamage of the Skin Through NF-κB Pathway In Vivo and In Vitro.Journal of cosmetic dermatology · 2025Article
- Autophagy-NADFrontiers in molecular biosciences · 2025Review
- Advances in research on potential therapeutic approaches for Niemann-Pick C1 disease.Frontiers in pharmacology · 2024Review
- Glycosphingolipids are linked to elevated neurotransmission and neurodegeneration in a Drosophila model of Niemann Pick type C.Disease models & mechanisms · 2023Article
- Lyso-globotriaosylsphingosine induces endothelial dysfunctionThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2023Article
- Outcomes of RIP Kinase Signaling During Neuroinvasive Viral Infection.Current topics in microbiology and immunology · 2023Review
- Organ Weights inInternational journal of molecular sciences · 2022Article
- Necroptosis in CNS diseases: Focus on astrocytes.Frontiers in aging neuroscience · 2022Review
- Expression of Ripk1 and DAM genes correlates with severity and progression of Krabbe disease.Human molecular genetics · 2021Article
- Gender-Specific Effects of Two Treatment Strategies in a Mouse Model of Niemann-Pick Disease Type C1.International journal of molecular sciences · 2021Article
- Article
- Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1.International journal of molecular sciences · 2021Review
- Understanding and Treating Niemann-Pick Type C Disease: Models Matter.International journal of molecular sciences · 2020Review
- Assessment of necroptosis in the retina in a repeated primary ocular blast injury mouse model.Experimental eye research · 2020Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Niemann-Pick disease, type C1 (NPC1) is a neurodegenerative, lysosomal storage disorder due to mutation of the NPC1 gene. The NPC1 phenotype is characterized by progressive neuronal dysfunction, including cerebellar ataxia and dementia. There is histological evidence of neuroinflammation and progressive neuronal loss, with cerebellar Purkinje cells particularly vulnerable to loss of NPC1 function. Necroptosis was evaluated as a mechanism of neuronal loss. Receptor-interacting protein kinase 1 (RIP1) and RIP3 are key components of the necrosomal complex that regulates necroptotic cell death. We report increased expression of RIP1 and RIP3 in NPC1 fibroblasts, NPC1 iPS cell-derived neuronal precursors, and in cerebellar tissue from both NPC1 mice and patients. Our data suggest a positive correlation between NPC1 neurological disease severity and assembly of the necrosome complex. Furthermore, we demonstrate that pharmacological inhibition of RIP1 decreases cell death both in vitro and in vivo. Treatment of Npc1-mutant mice with necrostatin-1, an allosteric inhibitor of RIP1, significantly delayed cerebellar Purkinje cell loss, progression of neurological symptoms, and death. Collectively, our data identified necroptosis as a key component of the molecular network that contributes to neuronal loss in NPC1 and establish that inhibition of necroptosis is a potential therapeutic intervention.
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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.