Ask about this productRelated genes to: C5AR1 Blocking Peptide
- Gene:
- C5AR1 NIH gene
- Name:
- complement C5a receptor 1
- Previous symbol:
- C5R1
- Synonyms:
- C5A, C5AR, CD88
- Chromosome:
- 19q13.32
- Locus Type:
- gene with protein product
- Date approved:
- 1991-12-04
- Date modifiied:
- 2016-08-10
Related products to: C5AR1 Blocking Peptide
Related articles to: C5AR1 Blocking Peptide
- Glioblastoma (GBM) is the most common and lethal primary malignant brain tumor in adults, with a median survival of approximately 15 months despite maximal multimodal therapy. The complement system plays a paradoxical dual role in GBM, mediating both antitumor immunity and immunosuppressive signaling within the tumor microenvironment, yet no systematic synthesis of complement-targeted therapeutic strategies exists. We aimed to comprehensively identify, appraise, and synthesize studies investigating complement-targeted therapies and complement-associated prognosis in GBM. Following PRISMA 2020 guidelines, we searched PubMed/MEDLINE and the Cochrane Library (CENTRAL) without date or language restrictions. Preclinical and clinical study designs were eligible. Risk of bias was assessed using SYRCLE, ROBINS-I, and study-type-specific checklists. Certainty of evidence was evaluated using GRADE. Statistical pooling was planned only for sufficiently comparable studies; clinical prognostic studies were synthesized narratively because they assessed non-equivalent constructs. Forty-one studies were included, comprising 15 preclinical in vivo, 13 preclinical in vitro, 6 clinical observational, and 7 bioinformatics studies. Five preclinical survival studies entered a structured quantitative synthesis, but no pooled cross-target effect was calculated because their interventions, comparators, and reported summary measures were non-equivalent. Clinical prognostic studies evaluated either individual protein biomarkers or multigene immune-risk signatures and were not pooled. GRADE certainty was "Very Low" for both outcomes. C3b opsonization and the C5a/C5aR1 axis were among the most frequently studied targets. Complement modulation remains a promising biological hypothesis in GBM rather than evidence for clinical application, and certainty of evidence is very low. Methodological and mechanistic heterogeneity across complement targets underscore the need for standardized preclinical models and randomized clinical trials. - Source: PubMed
Publication date: 2026/07/29
Walton Chase MStrickland Ben A - Microglial pro-inflammatory activation contributes to neuroinflammatory processes in many neurological disorders. Saturated fatty acids such as palmitic acid (PA) are increasingly recognized as inflammatory cues, yet the molecular mechanisms linking PA to microglial inflammatory responses remain incompletely defined. In this study, using BV-2 microglia as an exploratory in vitro model, we investigated whether C5aR1-sensitive signaling and JMJD3/H3K27me3-related epigenetic changes are involved in PA-associated inflammatory responses. PA exposure increased Iba1 expression, altered CD86/CD206 expression, and enhanced the secretion of IL-1β, IL-6 and TNF-α. Exogenous C5a produced broadly similar inflammatory changes. Under heat-inactivated serum conditions, PA increased cell-associated C5a immunoreactivity and extracellular C5a levels, and these C5a-related readouts were reduced by PMX53. PMX53 also attenuated PA-associated increases in inflammatory markers and in the expression of TLR4, total NF-κB p65, c-Fos, and c-Jun. In parallel, PA and C5a increased JMJD3 expression and JMJD3 enrichment at selected IL-1β and IL-6 promoter regions, accompanied by reduced H3K27me3 enrichment at these loci. Pharmacological KDM6 inhibition with GSK-J4 attenuated PA-associated increases in IL-1β and IL-6 expression. Together, these findings support the involvement of C5aR1-sensitive inflammatory signaling and JMJD3/H3K27me3-related epigenetic regulation in PA-associated microglial inflammatory responses. - Source: PubMed
Publication date: 2026/08/26
Chen LiqingXu SanqingLiu YanLuo Xiaoping - Activation of microglia and inflammatory response play a central role in the pathological process following intracerebral hemorrhage (ICH). In this study, single-nucleus transcriptomic and proteomic profiling was performed to investigate microglial changes after ICH. A significant upregulation of complement receptor C5aR1 was identified, particularly enriched in microglial subsets exhibiting a pro-inflammatory phenotype. The cellular localization and temporal expression dynamics of C5aR1 were validated by immunofluorescence staining, Western blotting, and quantitative PCR, demonstrating its sustained elevation in microglia after ICH. Pharmacological inhibition with the selective C5aR1 antagonist PMX205 markedly reduced the release of inflammatory cytokines, alleviated neuronal damage, and improved neurological function. Proteomic profiling and subsequent validation suggested that CCR5 may be associated with C5aR1-related inflammatory responses after ICH. Collectively, these findings suggest that C5aR1 serves as a regulatory factor in microglia-mediated neuroinflammation following ICH, and that targeting this pathway may offer a promising therapeutic strategy for hemorrhagic stroke. - Source: PubMed
Publication date: 2026/08/08
Shi XuanLi XueyanDing HaojieCao ChangLiu JialeLi ShuangkaiQiu YoujiaLi HaiyingLi Xiang - Enterovirus A71 (EV-A71), a member of the genus Enterovirus within the family Picornaviridae, induces neuroinflammation; however, the underlying mechanisms remain incompletely understood. This study demonstrates that the C5a-C5aR1 axis plays a pivotal role in EV-A71-induced blood-brain barrier (BBB) disruption and neuroinflammation, primarily by regulating neutrophil migration. Using human brain specimens and a mouse model, we observed pronounced inflammatory cell infiltration in the brainstem and BBB disruption following EV-A71 infection. Immunofluorescence analysis revealed robust activation of the C5a-C5aR1 axis in fatal EV-A71 cases. Notably, C5aR1 knockout (KO) mice displayed reduced Evans blue extravasation and preserved tight junction protein expression after infection. Immunopathological examination of fatal human cases further confirmed perivascular neutrophil (CD177⁺) infiltration in the brainstem. Importantly, C5aR1 deficiency significantly attenuated neutrophil accumulation and neutrophil extracellular trap (NET) release. Given that peptidylarginine deiminase 4 (PAD4) is a key enzyme driving NET formation, we generated neutrophil-specific PAD4 knockout mice (PAD4 Ne-KO) by crossing S100A8-Cre and PAD4fl/fl lines. As anticipated, neutrophil-specific PAD4 deletion or pharmacological NET blockade substantially ameliorated BBB injury and neuroinflammation following EV-A71 infection. Overall, our findings underscore a critical role for the C5a-C5aR1-neutrophil/NETs pathway in EV-A71 encephalitis pathogenesis and support its targeting as a therapeutic strategy for critically ill patients. - Source: PubMed
Publication date: 2026/08/05
Zhu PeiyuZeng XiaofengYuan XinLi ZijieJi WangquanLi DongSun TiantianYang HaiyanChen ShuaiyinLong JinzhaoWang FangZhang YaodongShen AdongZhang WeiguoJin YuefeiDuan Guangcai - Complement releases glutamate from the spinal cord glutamatergic synaptosomes through mechanisms involving amino-acid transporters (EAATs) and G protein coupled receptors (GPCRs), as suggested by the efficiency of the EAAT blocker dl-t-BOA and of entrapped Pertussis toxin (PTx) to half its releasing activity. The GPCR-mediated component involves C5aR1s since the C5aR1 non-competitive negative allosteric modulator DF2593A and the orthosteric antagonist W54011 concentration-dependently prevent the complement-evoked release of preloaded [H]D-aspartate. Antagonism, however, emerged only after the prolonged exposure of synaptosomes to these ligands, suggesting a multiple-phase model of receptor antagonism. Consistent with the involvement of this receptor, spinal cord synaptosomal lysates showed C5aR1 immunostaining corresponding to a dimeric assembly of the protein. We next examined mice suffering from the experimental autoimmune encephalomyelitis (EAE), at the acute stage of the disease (21 ± 1 days post immunization). Spinal cord homogenates from these mice show decreased MOG immunopositivity, suggestive of diffuse demyelination, but increased GFAP, vimentin, CD11b and CD45 staining, predictive of ongoing astrocytosis, microgliosis and infiltration of lymphocytes. These signs were paralleled by the overaccumulation of C1q, C3 and C5 components and increased C5aR1 staining, but conserved GLT1 one, in synaptosomal lysates. Lastly, the complement-evoked [H]D-Aspartate overflow from spinal cord synaptosomes was amplified when compared to controls, but still significantly reduced by DF2593A. These findings prove the existence of presynaptic release-regulating DF2593A-sensitive C5aR1s in spinal cord glutamatergic terminals, opening the road to therapeutic application of C5aR1 modulators to control symptoms associated with altered synaptic transmission during multiple sclerosis. - Source: PubMed
Publication date: 2026/07/30
Rosenwasser NicoleTorre VeronicaSaccani ParideOlivero GuendalinaBoccella SerenaBrandolini LauraPittaluga Anna