Figure 4. Regulation of synapse elimination in the mammalian CNS by the complement cascade.
An unidentified secreted signal from immature and reactive astrocytes upregulates expression of the complement component C1q in neurons. It is proposed that C1q binds to weaker synapses and tags them for elimination. This elimination might occur through phagocytosis by microglia, mediated by complement receptors at the surface of microglia. Other complement-cascade components such as C3 are also produced by glia in normal and disease conditions, and another possibility is that synapse elimination is triggered by C1q and C3 not only during development but also during the early stages of neurodegenerative diseases.