ArticleHuman molecular genetics2012
Neuronal and epithelial cell rescue resolves chronic systemic inflammation in the lipid storage disorder Niemann-Pick C.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 51 citations in OpenAlex.
- Efficacy of N-acetylcysteine in phenotypic suppression of mouse models of Niemann-Pick disease, type C1.Human molecular genetics · 2013Trial
- Biomarker Validation in NPC1: Foundations for Clinical Trials and Regulatory Alignment.Journal of inherited metabolic disease · 2025Review
- Deficiency of myeloid NPC1 exacerbates liver injury and fibrosis by impairing macrophage efferocytosis.Journal of advanced research · 2025Article
- Neuroinflammation and Lysosomal Abnormalities Characterise the Essential Role for Oxidation Resistance 1 in the Developing and Adult Cerebellum.Antioxidants (Basel, Switzerland) · 2024Article
- Sterol O-Acyltransferase 1 (International journal of molecular sciences · 2024Article
- Differently increased volumes of multiple brain areas inFrontiers in neuroanatomy · 2024Article
- Article
- Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine.NPJ genomic medicine · 2023Review
- Exploring Pro-Inflammatory Immunological Mediators: Unraveling the Mechanisms of Neuroinflammation in Lysosomal Storage Diseases.Biomedicines · 2023Review
- Identification of cerebral spinal fluid protein biomarkers in Niemann-Pick disease, type C1.Biomarker research · 2023Article
- Article
- Loss of NPC1 enhances phagocytic uptake and impairs lipid trafficking in microglia.Nature communications · 2021Article
- Dietary plant stanol ester supplementation reduces peripheral symptoms in a mouse model of Niemann-Pick type C1 disease.Journal of lipid research · 2020Article
- Evaluation of the Potential Role of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Niemann-Pick Disease, Type C1.International journal of molecular sciences · 2020Article
- Complement Component C3 Participates in Early Stages of Niemann-Pick C Mouse Liver Damage.International journal of molecular sciences · 2020Article
- Identification of Novel Pathways Associated with Patterned Cerebellar Purkinje Neuron Degeneration in Niemann-Pick Disease, Type C1.International journal of molecular sciences · 2019Article
- Gadolinium Chloride Rescues Niemann⁻Pick Type C Liver Damage.International journal of molecular sciences · 2018Article
- Microglia activation in Niemann-Pick disease, type C1 is amendable to therapeutic intervention.Human molecular genetics · 2018Article
- The Extending Spectrum of NPC1-Related Human Disorders: From Niemann-Pick C1 Disease to Obesity.Endocrine reviews · 2018Review
- Deletion of MCP-1 Impedes Pathogenesis of Acid Ceramidase Deficiency.Scientific reports · 2018Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Chronic systemic inflammation is thought to be a major contributor to metabolic and neurodegenerative diseases. Since inflammatory components are shared among different disorders, targeting inflammation is an attractive option for mitigating disease. To test the significance of inflammation in the lipid storage disorder (LSD) Niemann-Pick C (NPC), we deleted the macrophage inflammatory gene Mip1a/Ccl3 from NPC diseased mice. Deletion of Ccl3 had been reported to delay neuronal loss in Sandhoff LSD mice by inhibiting macrophage infiltration. For NPC mice, in contrast, deleting Ccl3 did not retard neurodegeneration and worsened the clinical outcome. Depletion of visceral tissue macrophages also did not alter central nervous system (CNS) pathology and instead increased liver injury, suggesting a limited macrophage infiltration response into the CNS and a beneficial role of macrophage activity in visceral tissue. Prevention of neuron loss or liver injury, even at late stages in the disease, was achieved through specific rescue of NPC disease in neurons or in liver epithelial cells, respectively. Local epithelial cell correction was also sufficient to reduce the macrophage-associated pathology in lung tissue. These results demonstrate that elevated inflammation and macrophage activity does not necessarily contribute to neurodegeneration and tissue injury, and LSD defects in immune cells may not preclude an appropriate inflammatory response. We conclude that inflammation remains secondary to neuronal and epithelial cell dysfunction and does not irreversibly contribute to the pathogenic cascade in NPC disease. Without further exploration of possible beneficial roles of inflammatory mediators, targeting inflammation may not be therapeutically effective at ameliorating disease severity.
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Registered trials
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