Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Niemann-Pick type C disease is a rare neurodegenerative disorder mainly caused by mutations in NPC1, resulting in abnormal late endosomal/lysosomal lipid storage. Although microgliosis is a prominent pathological feature, direct consequences of NPC1 loss on microglial function remain not fully characterized. We discovered pathological proteomic signatures and phenotypes in NPC1-deficient murine models and demonstrate a cell autonomous function of NPC1 in microglia. Loss of NPC1 triggers enhanced phagocytic uptake and impaired myelin turnover in microglia that precede neuronal death. Npc1 microglia feature a striking accumulation of multivesicular bodies and impaired trafficking of lipids to lysosomes while lysosomal degradation function remains preserved. Molecular and functional defects were also detected in blood-derived macrophages of NPC patients that provide a potential tool for monitoring disease. Our study underscores an essential cell autonomous role for NPC1 in immune cells and implies microglial therapeutic potential.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904859 | PMC |
| http://dx.doi.org/10.1038/s41467-021-21428-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Role of mTORC1 signaling in postnatal microglia activation preceding neurodegeneration in a mouse model for Niemann-Pick disease Type C.
PLoS One
September 2025
Department of Biology, Providence College, Providence, Rhode Island, United States of America.
In Npc1 deficient mice, postnatal developmental alterations in cerebellar microglia and Purkinje cells (PCs) are followed by early-onset neurodegeneration. Even in the absence of PC loss, microglia in Npc1nmf164 mice display hallmark features of activation during early postnatal development, including increased proliferation, enhanced phagocytic activity, and morphological changes indicative of an activated state. In this study, we investigated whether mammalian target of rapamycin complex 1 (mTORC1) drives postnatal activation of cerebellar microglia in Npc1nmf164 mice.
View Article and Find Full Text PDFKetogenic Diet in Niemann-Pick Type C: Insights From a Case Report.
Int J Dev Neurosci
October 2025
Department of Inherited Metabolic Disorders, Dokuz Eylul University Faculty of Medicine, Izmir, Turkey.
Niemann-Pick disease type C (NPC) is a lysosomal storage disorder characterized by progressive neurological deterioration. Although there is no curative treatment, early initiation of miglustat, prior to significant neurological decline, may slow disease progression. This case report describes a patient whose initial symptoms emerged around age 9 and who was diagnosed with NPC at age 14 following gradual neurological decline.
View Article and Find Full Text PDFMenstrual blood-derived endometrial stem cells ameliorate neuroinflammation and apoptosis through JAK2/STAT3 signaling pathway in NPC1 mutant cell and mice.
Stem Cell Res Ther
August 2025
Stem Cell and Biotherapy Technology Research Center of Henan, School of Life Science and Technology, Xinxiang Medical University, Xinxiang, 453003, Henan, China.
Background: Niemann-Pick disease type C1 (NPC1) is caused by NPC1 gene mutations, resulting in Purkinje cell degeneration and death, glial cell activation, and progressive neurodegeneration. Menstrual blood-derived endometrial stem cells (MenSCs) have been explored as a promising tool for treating neurodegenerative diseases due to their wide range of sources, non-invasive nature, and regular collection methods.
Objectives: This study aims to investigate whether MenSCs can improve neuroinflammation and apoptosis in NPC1 mutant cell (Npc1 BV2 cell line) and mice (Npc1 mice), and explore their underlying mechanisms.
Heterozygosity in NPC may be associated with neurologic and systemic phenotypes.
Front Neurol
August 2025
INSPIRE-PNRM+, Neuroimaging Center (NIC), University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Background: Niemann-Pick disease type C (NPC) is a pan-ethnic, progressive, recessively inherited lysosomal disorder that affects 1:100,000 live births. Emerging biochemical, genetic, and clinical evidence challenges the traditional view that disease-associated variants in the genes associated with the typical phenotype NPC manifest as an exclusively autosomal recessive disorder. While biallelic pathogenic variants cause the NPC disease phenotype, heterozygous carriers may exhibit phenotypic traits attributable to a partial loss of or function.
View Article and Find Full Text PDFBiomarker Validation in NPC1: Foundations for Clinical Trials and Regulatory Alignment.
J Inherit Metab Dis
September 2025
Division of Translational Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, DHHS, Bethesda, Maryland, USA.
Niemann-Pick Type C1 (NPC1) disease is a rare, autosomal recessive, neurovisceral lysosomal storage disorder caused by mutations in the NPC1. This condition leads to defective intracellular cholesterol and lipid trafficking, resulting in the accumulation of unesterified cholesterol and glycosphingolipids in late endosomes and lysosomes. Clinically, NPC1 manifests with a heterogeneous spectrum of progressive neurological symptoms, including ataxia, vertical supranuclear gaze palsy, dysarthria, cognitive decline, and dystonia, often accompanied by systemic signs such as hepatosplenomegaly and neonatal cholestasis.
View Article and Find Full Text PDF