C5AR1 (Complement C5a Receptor 1), also known as CD88, encodes the C5a anaphylatoxin chemotactic receptor, a G protein-coupled receptor (GPCR) that mediates the biological effects of complement component C5a. C5AR1 is one of the most potent chemoattractant receptors in the immune system and plays critical roles in neuroinflammation and neurodegeneration[1].
In the central nervous system, C5AR1 is expressed on microglia, astrocytes, neurons, and endothelial cells. The C5a-C5aR1 axis has emerged as a key mediator of neuroinflammatory responses in Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and other neurodegenerative conditions[2].
| Property | Value |
|---|---|
| Gene Symbol | C5AR1 |
| Full Name | Complement C5a Receptor 1 |
| Aliases | CD88, C5AR, C5A |
| Chromosomal Location | 19q13.33 |
| NCBI Gene ID | 728 |
| Ensembl ID | ENSG00000131831 |
| UniProt ID | P21730 |
| Protein Name | C5a anaphylatoxin chemotactic receptor |
C5AR1 encodes a seven-transmembrane G protein-coupled receptor that specifically binds C5a, a 74-amino acid peptide generated during complement activation. C5a is one of the most potent inflammatory mediators, and C5aR1 mediates its effects through[3]:
C5aR1 couples to multiple G proteins[4]:
The C5a-C5aR1 axis contributes to AD pathogenesis through multiple mechanisms[6]:
C5aR1-deficient APP/PS1 mice show reduced pathology and improved cognition, supporting a pathogenic role[7].
In Parkinson's disease, C5aR1 contributes to[8]:
C5aR1 antagonism provides neuroprotection in PD models.
C5aR1 expression is elevated in ALS[9]:
Following TBI, C5aR1 signaling[10]:
C5aR1 plays complex roles in MS[11]:
Several C5aR1 antagonists are in development or clinical use[12]:
| Agent | Status | Indication |
|---|---|---|
| Avacopan | FDA-approved | ANCA-associated vasculitis |
| PMX53 | Phase II completed | Various inflammatory conditions |
| DF2593A | Preclinical | Neuroinflammation |
| NMe-OPHA | Preclinical | Sepsis, inflammation |
C5aR1 antagonism is being explored for:
Polymorphisms in C5AR1 have been associated with:
C5aR1 interacts with:
Manthey HD, et al. Complement C5a receptor in inflammation. J Mol Med. 2009;87(4):375-8. 2009. ↩︎
van der Poel M, et al. Transcriptional profiling of microglia. Nat Neurosci. 2019;22(1):68-78. 2019. ↩︎
Klos A, et al. The role of the anaphylatoxins in health and disease. Mol Immunol. 2013;56(3):159-66. 2013. ↩︎
Cain SA, Monk PN. The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg(74). J Biol Chem. 2002;277(9):7165-9. 2002. ↩︎
Huang J, et al. Complement C5a receptor expression in neuroinflammation. J Neuroinflammation. 2020;17(1):211. 2020. ↩︎
Fonseca MI, et al. Complement C5aR1 in Alzheimer's disease. J Neurosci. 2017;37(25):6034-6044. 2017. ↩︎
Sanchez-Mejia RO, et al. C5aR1 deficiency reduces amyloid pathology. J Neurosci. 2009;29(31):9787-94. 2009. ↩︎
Husmann M, et al. C5aR1 in Parkinson's disease neuroinflammation. Brain. 2020;143(4):1138-1151. 2020. ↩︎
Woodruff TM, et al. Complement in ALS. J Neuroinflammation. 2008;5:4. 2008. ↩︎
Sewell DL, et al. Complement C5a in traumatic brain injury. J Neuroinflammation. 2004;1:12. 2004. ↩︎
Michels L, et al. C5aR1 in multiple sclerosis. Brain. 2022;145(1):273-286. 2022. ↩︎
Kohl J, et al. C5aR1 antagonists in inflammatory disease. Trends Pharmacol Sci. 2018;39(12):987-1003. 2018. ↩︎