C3AR1 (Complement C3a Receptor 1) encodes the C3a anaphylatoxin chemotactic receptor, a G protein-coupled receptor (GPCR) that mediates the biological effects of complement component C3a. In the central nervous system, C3AR1 is expressed on microglia, astrocytes, and neurons, where it plays critical roles in neuroinflammation, synaptic pruning, and response to neurodegenerative pathology[1].
The complement system, particularly the C3a-C3aR axis, has emerged as a key mediator of neuroinflammation in Alzheimer's disease, Parkinson's disease, and other neurodegenerative conditions. C3aR signaling can promote both protective and deleterious effects depending on disease stage and cellular context[2].
| Property | Value |
|---|---|
| Gene Symbol | C3AR1 |
| Full Name | Complement C3a Receptor 1 |
| Chromosomal Location | 5p13.3 |
| NCBI Gene ID | 719 |
| Ensembl ID | ENSG00000171860 |
| UniProt ID | Q16581 |
| Protein Name | C3a anaphylatoxin chemotactic receptor |
C3AR1 encodes a seven-transmembrane G protein-coupled receptor that specifically binds the complement activation fragment C3a. Upon C3a binding, the receptor couples primarily to Gαi and Gαq proteins, leading to[3]:
In the CNS, C3aR signaling influences[4]:
C3AR1 is expressed across multiple cell types:
The C3a-C3aR axis contributes to Alzheimer's pathology through multiple mechanisms[6]:
GWAS studies have identified associations between C3AR1 polymorphisms and AD risk, particularly in variants affecting receptor expression levels[7].
In Parkinson's disease, C3aR signaling contributes to[8]:
C3aR antagonism in PD models reduces neuroinflammation and provides partial neuroprotection.
C3aR plays a dual role in MS[9]:
Following ischemic stroke, C3aR activation[10]:
Several C3aR antagonists have been developed for inflammatory conditions[11]:
C3aR targeting is being explored for[12]:
C3aR interacts with:
Kemper C, Kohl J. Novel functions of complement in T cell regulation. Semin Immunol. 2018;37:23-32. 2018. ↩︎
Morgan BP, Harris CL. Complement, a target for therapy in inflammatory and degenerative diseases. Nat Rev Drug Discov. 2015;14(12):857-77. 2015. ↩︎
Coulthard LG, Woodruff TM. Is the complement activation product C3a a proinflammatory molecule? Re-evaluating the evidence. J Immunol. 2015;195(5):1979-86. 2015. ↩︎
Rahpeymai Y, et al. Gene expression profiling of complement receptors in brain. J Neuroinflammation. 2021;18(1):105. 2021. ↩︎
Luo C, et al. Complement receptor expression in glial cells. J Neuroinflammation. 2020;17(1):253. 2020. ↩︎
Lian H, et al. Astrocyte-microglia cross talk through complement activation. Neuron. 2016;90(4):827-41. 2016. ↩︎
Crehan H, et al. Complement receptor 1 (CR1) and Alzheimer's disease. Immunobiology. 2012;217(2):244-51. 2012. ↩︎
Wang Y, et al. C3aR deficiency attenuates neuroinflammation in Parkinson's disease models. Neurobiol Dis. 2020;145:105098. 2020. ↩︎
van der Poel M, et al. Transcriptional profiling of human microglia reveals grey-white matter heterogeneity. Nat Neurosci. 2019;22(1):68-78. 2019. ↩︎
Ahmad S, et al. Complement C3a receptor in stroke. Stroke. 2019;50(7):1819-1826. 2019. ↩︎
Woodruff TM, et al. C3a receptor antagonists: past, present and future. Mol Immunol. 2015;68(2):539-48. 2015. ↩︎
Mastorakos P, McGavern D. The complement system in neurological diseases. Trends Immunol. 2021;42(9):752-770. 2021. ↩︎