Complement cascades and brain disorders

The complement system is a vital component of innate immunity. Besides its roles in pathogen defense, its significance in neurodevelopment, neurodegeneration, and cancer progression is beginning to be recognized. We performed a comprehensive literature review to summarize the involvement and dysregulation of the complement system in three main CNS-associated conditions: Alzheimer's disease, schizophrenia, and glioma. In Alzheimer's disease, activation of the complement system contributes to neuroinflammation, synaptic loss, and neuronal death. In glioblastoma, complement promotes tumor growth, immune evasion, and therapy resistance. In schizophrenia, genetic variations in complement components, particularly C4A, are associated with synaptic pruning abnormalities and disease susceptibility. We conclude that the complement system has a dual role of protector and pathogenic mediator in the central nervous system. While it is critical in neurodegenerative, oncological, and psychiatric disorders, its role is not understood well enough. For therapeutic purposes, targeting the complement system may open new frontiers for therapeutic interventions without disrupting important physiological processes. More research is needed to elucidate the exact roles of the complement and help translate these findings into clinical settings.