Complement component 4A (C4A) (C4A)

Complement component 4A (C4A) is a central protein in the classical complement cascade that has emerged as a key driver of the C4A-mediated neuroimmune pathway, particularly in the context of brain development and psychiatric disorders. In the central nervous system, C4A is expressed by neurons and glia and localizes to synapses, where it facilitates synaptic pruning by tagging specific connections for elimination by microglial cells (Sekar et al., 2016, Nature). Genetic evidence has established that high-expression variants and increased copy numbers of the C4A gene are the strongest common genetic risk factors for schizophrenia, likely due to excessive synapse loss during adolescence (Sellgren et al., 2019, Nature Communications). Beyond its role in the brain, C4A is a critical component of the systemic innate immune system, involved in the opsonization of pathogens and the clearance of apoptotic debris (UniProt P0C0L4). Because C4A deficiency is a known risk factor for systemic lupus erythematosus (SLE), therapeutic strategies must carefully balance the inhibition of neurotoxic synaptic pruning with the maintenance of peripheral immune competence and self-tolerance (Presumey et al., 2017, Trends in Molecular Medicine). Current experimental approaches include the use of monoclonal antibodies and antisense oligonucleotides to selectively modulate C4A levels or activity.

Other names

C4AComplement C4-ACO4AAcidic complement C4C4A1C4A2C4A3C4A4C4A6

Inhibition of the classical complement cascade to reduce microglial-mediated synaptic engulfment and neuroinflammation.