Complement C1q subcomponent subunit A mRNA (C1QA mRNA)

Complement C1q subcomponent subunit A (C1QA) mRNA is the transcript responsible for the synthesis of the A-chain of the C1q protein, the initiating component of the classical complement cascade (UniProt P02745). C1q is a large, multimeric protein composed of 18 polypeptide chains (six A, six B, and six C chains) that recognizes and binds to antibodies or pathogens to trigger immune responses (NCBI Gene 712). In the central nervous system, C1QA mRNA is primarily expressed by microglia and is significantly upregulated during aging and in neurodegenerative diseases (Stevens et al., 2007). This upregulation leads to excessive C1q-mediated synaptic pruning, contributing to the cognitive decline seen in Alzheimer's disease and the vision loss in glaucoma (Hong et al., 2016). Therapeutic strategies targeting C1QA mRNA, such as antisense oligonucleotides or siRNA, aim to reduce C1q protein levels at the source to prevent pathological complement activation while potentially avoiding some systemic side effects of broad complement inhibition. However, complete suppression of C1q poses risks, including increased susceptibility to infections and the development of autoimmune conditions like systemic lupus erythematosus due to impaired debris clearance (Annexon Biosciences). Clinical candidates like ANX005 currently target the C1q protein product, but mRNA-directed approaches remain an active area of preclinical research for chronic neuroinflammation.

Other names

Complement component 1, q subcomponent, A chain mRNAC1QAComplement C1q subunit AComplement component 1, q subcomponent, alpha polypeptide

RNA interference (siRNA), Antisense inhibition (ASO), Prevention of C1q protein assembly