Aberrant Complement System Activation in Neurological Disorders

Int J Mol Sci. 2021 Apr 28;22(9):4675. doi: 10.3390/ijms22094675.


The complement system is an assembly of proteins that collectively participate in the functions of the healthy and diseased brain. The complement system plays an important role in the maintenance of uninjured (healthy) brain homeostasis, contributing to the clearance of invading pathogens and apoptotic cells, and limiting the inflammatory immune response. However, overactivation or underregulation of the entire complement cascade within the brain may lead to neuronal damage and disturbances in brain function. During the last decade, there has been a growing interest in the role that this cascading pathway plays in the neuropathology of a diverse array of brain disorders (e.g., acute neurotraumatic insult, chronic neurodegenerative diseases, and psychiatric disturbances) in which interruption of neuronal homeostasis triggers complement activation. Dysfunction of the complement promotes a disease-specific response that may have either beneficial or detrimental effects. Despite recent advances, the explicit link between complement component regulation and brain disorders remains unclear. Therefore, a comprehensible understanding of such relationships at different stages of diseases could provide new insight into potential therapeutic targets to ameliorate or slow progression of currently intractable disorders in the nervous system. Hence, the aim of this review is to provide a summary of the literature on the emerging role of the complement system in certain brain disorders.

Keywords: Huntington disease; Parkinson’s disease; amyotrophic lateral sclerosis; autism; cerebral ischaemia; complement system; epilepsy; multiple sclerosis; neurodegenerative diseases; schizophrenia; spinal cord injury; traumatic brain injury.

Publication types

  • Review