Topic
Complement system
About: Complement system is a research topic. Over the lifetime, 13510 publications have been published within this topic receiving 578106 citations. The topic is also known as: complement.
Papers published on a yearly basis
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Papers
TL;DR: An updated view of the function, structure and dynamics of the complement network is described, its interconnection with immunity at large and with other endogenous pathways is highlighted, and its multiple roles in homeostasis and disease are illustrated.
Abstract: Nearly a century after the significance of the human complement system was recognized, we have come to realize that its functions extend far beyond the elimination of microbes. Complement acts as a rapid and efficient immune surveillance system that has distinct effects on healthy and altered host cells and foreign intruders. By eliminating cellular debris and infectious microbes, orchestrating immune responses and sending 'danger' signals, complement contributes substantially to homeostasis, but it can also take action against healthy cells if not properly controlled. This review describes our updated view of the function, structure and dynamics of the complement network, highlights its interconnection with immunity at large and with other endogenous pathways, and illustrates its multiple roles in homeostasis and disease.
3,488 citations
TL;DR: It is shown that C1q, the initiating protein in the classical complement cascade, is expressed by postnatal neurons in response to immature astrocytes and is localized to synapses throughout the postnatal CNS and retina, supporting a model in which unwanted synapses are tagged by complement for elimination and suggesting that complement-mediated synapse elimination may become aberrantly reactivated in neurodegenerative disease.
3,020 citations
TL;DR: In mouse models, the complement-dependent pathway and microglia that prune excess synapses in development are inappropriately activated and mediate synapse loss in AD, which is an early feature of Alzheimer's disease and correlates with cognitive decline.
Abstract: Synapse loss in Alzheimer’s disease (AD) correlates with cognitive decline. Involvement of microglia and complement in AD has been attributed to neuroinflammation, prominent late in disease. Here we show in mouse models that complement and microglia mediate synaptic loss early in AD. C1q, the initiating protein of the classical complement cascade, is increased and associated with synapses before overt plaque deposition. Inhibition of C1q, C3, or the microglial complement receptor CR3 reduces the number of phagocytic microglia, as well as the extent of early synapse loss. C1q is necessary for the toxic effects of soluble β-amyloid (Aβ) oligomers on synapses and hippocampal long-term potentiation. Finally, microglia in adult brains engulf synaptic material in a CR3-dependent process when exposed to soluble Aβ oligomers. Together, these findings suggest that the complement-dependent pathway and microglia that prune excess synapses in development are inappropriately activated and mediate synapse loss in AD.
2,759 citations
TL;DR: Characterization of the nonclonal receptors of the innate immune system responsible for the adjuvant activity, and, evidently, for the associated side effects, would provide a powerful alternative approach, which would ultimately allow one to target these receptors directly.
2,609 citations
TL;DR: In this paper, single-nucleotide polymorphisms were tested for association with AMD in two independent case-control populations and significant association was identified within the regulation of complement activation locus and was centered over a tyrosine-402 --> histidine-402 protein polymorphism in the gene encoding complement factor.
Abstract: Age-related macular degeneration (AMD) is a common, late-onset, and complex trait with multiple risk factors Concentrating on a region harboring a locus for AMD on 1q25-31, the ARMD1 locus, we tested single-nucleotide polymorphisms for association with AMD in two independent case-control populations Significant association (P = 495 x 10(-10)) was identified within the regulation of complement activation locus and was centered over a tyrosine-402 --> histidine-402 protein polymorphism in the gene encoding complement factor H Possession of at least one histidine at amino acid position 402 increased the risk of AMD 27-fold and may account for 50% of the attributable risk of AMD
2,426 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2026 | 1 |
| 2025 | 220 |
| 2024 | 329 |
| 2023 | 522 |
| 2022 | 807 |
| 2021 | 540 |