ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Anatomically defined neuron-based rescue of neurodegenerative Niemann-Pick type C disorder.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 106 citations in OpenAlex.
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- Article
- 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
- Intracerebroventricular administration of a modified hexosaminidase ameliorates late-stage neurodegeneration in a GM2 mouse model.PloS one · 2025Article
- Differential roles of lysosomal cholesterol transporters in the development ofLife science alliance · 2024Article
- Mutant induced neurons and humanized mice enable identification of Niemann-Pick type C1 proteostatic therapies.JCI insight · 2024Article
- Endo-lysosomal dysfunction and neuronal-glial crosstalk in Niemann-Pick type C disease.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Overlapping Neuroimmune Mechanisms and Therapeutic Targets in Neurodegenerative Disorders.Biomedicines · 2023Review
- Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine.NPJ genomic medicine · 2023Review
- Species-specific differences in NPC1 protein trafficking govern therapeutic response in Niemann-Pick type C disease.JCI insight · 2022Article
- TDP-43 proteinopathy occurs independently of autophagic substrate accumulation and underlies nuclear defects in Niemann-Pick C disease.Neuropathology and applied neurobiology · 2021Article
- Treatment trials in Niemann-Pick type C disease.Metabolic brain disease · 2021Review
- Article
- Neurodegeneration in Niemann-Pick Type C Disease: An Updated Review on Pharmacological and Non-Pharmacological Approaches to Counteract Brain and Cognitive Impairment.International journal of molecular sciences · 2021Review
- Loss of NPC1 enhances phagocytic uptake and impairs lipid trafficking in microglia.Nature communications · 2021Article
- Understanding and Treating Niemann-Pick Type C Disease: Models Matter.International journal of molecular sciences · 2020Review
- Signatures of natural selection and ethnic-specific prevalence of NPC1 pathogenic mutations contributing to obesity and Niemann-Pick disease type C1.Scientific reports · 2020Article
- Complement Component C3 Participates in Early Stages of Niemann-Pick C Mouse Liver Damage.International journal of molecular sciences · 2020Article
- Cerebellar Astrocytes: Much More Than Passive Bystanders In Ataxia Pathophysiology.Journal of clinical medicine · 2020Review
- Cytosine and adenine base editing of the brain, liver, retina, heart and skeletal muscle of mice via adeno-associated viruses.Nature biomedical engineering · 2020Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
Niemann-Pick type C disease is a fatal lysosomal storage disorder caused by loss of NPC1 function. The disorder severely affects multiple body systems, particularly the nervous system. To test whether rescue of NPC1 activity in neurons, astrocytes, or other cell types can correct the neurological defects, a Tet-inducible Npc1-YFP transgene was introduced into Npc1(-/-) mice for the cell type-specific rescue of NPC1 loss. NPC1-YFP produced in neurons prevented neuron degeneration, slowed reactive glial activity, and ameliorated the disease. NPC1-YFP produced in astrocytes or in cells of visceral tissue did not. These results suggest that loss of NPC1 activity from neurons is the primary cause of the neuropathology and that rescue of NPC1 function in neurons is sufficient to mitigate the disease. The ability of neurons to survive and function in a cell-autonomous fashion allowed the use of this newly engineered rescue system to further define the brain regions or neuron populations required to ameliorate a neurological symptom. NPC1-YFP produced specifically in cerebellar Purkinje neurons reduced ataxia, increased weight, and prolonged life, but it did not prevent the eventual decline and premature death of Npc1(-/-) mice. Significant increase in lifespan correlated with sustained reduction of inflammation in the thalamus. Neuron rescue of other forebrain areas provided little benefit. Future work targeting increasingly discrete neuronal networks should reveal which CNS areas are critical for survival. This work may have broad implications for understanding the anatomical and cellular basis of neurological signs and symptoms of other neurodegenerative and lysosomal disorders.
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