ArticleJournal of neuroinflammation2012
Complement is dispensable for neurodegeneration in Niemann-Pick disease type C.
Article in Journal of neuroinflammation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 41 citations in OpenAlex.
- Complement System and Adhesion Molecule Skirmishes in Fabry Disease: Insights into Pathogenesis and Disease Mechanisms.International journal of molecular sciences · 2024Review
- Sterol O-Acyltransferase 1 (International journal of molecular sciences · 2024Article
- Understanding the phenotypic variability in Niemann-Pick disease type C (NPC): a need for precision medicine.NPJ genomic medicine · 2023Review
- A differential proteomics study of cerebrospinal fluid from individuals with Niemann-Pick disease, Type C1.Proteomics · 2023Article
- Exploring Pro-Inflammatory Immunological Mediators: Unraveling the Mechanisms of Neuroinflammation in Lysosomal Storage Diseases.Biomedicines · 2023Review
- Microglia as hackers of the matrix: sculpting synapses and the extracellular space.Cellular & molecular immunology · 2021Review
- Complement-associated loss of CA2 inhibitory synapses in the demyelinated hippocampus impairs memory.Acta neuropathologica · 2021Article
- Loss of NPC1 enhances phagocytic uptake and impairs lipid trafficking in microglia.Nature communications · 2021Article
- Toll-like receptor mediated lysozyme expression in Niemann-pick disease, type C1.Molecular genetics and metabolism · 2020Article
- Single Cell Transcriptome Analysis of Niemann-Pick Disease, Type C1 Cerebella.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
- Unique molecular signature in mucolipidosis type IV microglia.Journal of neuroinflammation · 2019Article
- Alteration of GABAergic Input Precedes Neurodegeneration of Cerebellar Purkinje Cells of NPC1-Deficient Mice.International journal of molecular sciences · 2019Article
- Differential Proteomics Reveals miR-155 as a Novel Indicator of Liver and Spleen Pathology in the Symptomatic Niemann-Pick Disease, Type C1 Mouse Model.Molecules (Basel, Switzerland) · 2019Article
- Proteomics of the corpus callosum to identify novel factors involved in hypomyelinated Niemann-Pick Type C disease mice.Molecular brain · 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
- Impact of Reduced Cerebellar EAAT Expression on Purkinje Cell Firing Pattern of NPC1-deficient Mice.Scientific reports · 2018Article
- Complement component 3 (C3) expression in the hippocampus after excitotoxic injury: role of C/EBPβ.Journal of neuroinflammation · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe immune system has been implicated in neurodegeneration during development and disease. In various studies, the absence of complement (that is, C1q deficiency) impeded the elimination of apoptotic neurons, allowing survival. In the genetic lysosomal storage disease Niemann-Pick C (NPC), caused by loss of NPC1 function, the expression of complement system components, C1q especially, is elevated in degenerating brain regions of Npc1-/- mice. Here we test whether complement is mediating neurodegeneration in NPC disease.
findingsIn normal mature mice, C1q mRNA was found in neurons, particularly cerebellar Purkinje neurons (PNs). In Npc1-/- mice, C1q mRNA was additionally found in activated microglia, which accumulate during disease progression and PN loss. Interestingly, C1q was not enriched on or near degenerating neurons. Instead, C1q was concentrated in other brain regions, where it partially co-localized with a potential C1q inhibitor, chondroitin sulfate proteoglycan (CSPG). Genetic deletion of C1q, or of the downstream complement pathway component C3, did not significantly alter patterned neuron loss or disease progression. Deletion of other immune response factors, a Toll-like receptor, a matrix metalloprotease, or the apoptosis facilitator BIM, also failed to alter neuron loss.
conclusionWe conclude that complement is not involved in the death and clearance of neurons in NPC disease. This study supports a view of neuroinflammation as a secondary response with non-causal relationship to neuron injury in the disease. This disease model may prove useful for understanding the conditions in which complement and immunity do contribute to neurodegeneration in other disorders.
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