ArticleHuman molecular genetics2018
Microglia activation in Niemann-Pick disease, type C1 is amendable to therapeutic intervention.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
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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.
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Who cites it
56 citing papers in PubMed, 78 citations in OpenAlex.
- 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
- A model of free sialic acid storage disorder reveals hypomyelinating leukodystrophy and Purkinje cell degeneration.Disease models & mechanisms · 2026Article
- Optimization of systemic AAV9 gene therapy in Niemann-Pick disease, type C1 mice.Life science alliance · 2026Article
- Article
- Molecular and histological characterizations reveal two distinct senescent microglia populations in Niemann-Pick disease type C mouse model.GeroScience · 2026Article
- From autophagy-lysosomal deficits to neurodegeneration in Niemann-Pick type C1 disease: implications for age-related neurodegenerative disorders.Frontiers in neuroscience · 2026Review
- Cholesterol Depletion with U18666A and Methyl-β Cyclodextrin Increased Small Molecule Permeability Across Brain Microvascular Endothelial Cells.Annals of biomedical engineering · 2025Article
- Mesoscale volumetric fluorescence imaging at nanoscale resolution by photochemical sectioning.Science (New York, N.Y.) · 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
- Combined treatment of Ketogenic diet and propagermanium reduces neuroinflammation in Tay-Sachs disease mouse model.Metabolic brain disease · 2025Article
- CD22 modulation alleviates amyloid β-induced neuroinflammation.Journal of neuroinflammation · 2025Article
- 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
- Article
- Instationary metabolic flux analysis reveals that NPC1 inhibition increases glycolysis and decreases mitochondrial metabolism in brain microvascular endothelial cells.Neurobiology of disease · 2025Article
- NPC1 links cholesterol trafficking to microglial morphology via the gastrosome.Nature communications · 2024Article
- Essential Oil Constituents as Anti-Inflammatory and Neuroprotective Agents: An Insight through Microglia Modulation.International journal of molecular sciences · 2024Review
- CD22 blockade aggravates EAE and its role in microglia polarization.CNS neuroscience & therapeutics · 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
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Niemann-Pick disease, type C1 (NPC1) is a neurodegenerative disorder with limited treatment options. NPC1 is associated with neuroinflammation; however, attempts to therapeutically target neuroinflammation in NPC1 have had mixed success. We show here that NPC1 neuroinflammation is characterized by an atypical microglia activation phenotype. Specifically, Npc1-/- microglia demonstrated altered morphology, reduced levels of lineage markers and a shift toward glycolytic metabolism. Treatment with 2-hydroxypropyl-β-cyclodextrin (HPβCD), a drug currently being studied in a phase 2b/3 clinical trial, reversed all microglia-associated defects in Npc1-/- animals. In addition, impairing microglia mediated neuroinflammation by genetic deletion of IRF8 led to decreased symptoms and increased lifespan. We identified CD22 as a marker of dysregulated microglia in Npc1 mutant mice and subsequently demonstrated that elevated cerebrospinal fluid levels of CD22 in NPC1 patients responds to HPβCD administration. Collectively, these data provide the first in-depth analysis of microglia function in NPC1 and suggest possible new therapeutic approaches.
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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.