Activation of complement in the central nervous system: roles in neurodegeneration and neuroprotection.
The complement system is an essential effector of the humoral and cellular immunity involved in cytolysis and immune/inflammatory responses. Complement participates in host defense against pathogens by triggering the formation of the membrane attack complex. Complement opsonins (C1q, C3b, and iC3b) interact with surface complement receptors to promote phagocytosis, whereas complement anaphylatoxins C3a and C5a initiate local inflammatory responses that ultimately contribute to the protection and healing of the host. However, activation of complement to an inappropriate extent has been proposed to promote tissue injury. There is now compelling evidence that complement activation in the brain is a double-edged sword in that it can exert beneficial or detrimental effects depending on the pathophysiological context. This review focuses on the roles of the complement system in the pathogenesis of acute brain injury (cerebral ischemia and trauma) and chronic neurodegeneration (Alzheimer's disease). Because many effects of the complement appear to promote neuronal survival and tissue remodeling, directing activation of the complement system in the brain may provide a better therapeutic rationale than inhibiting it.
van Beek
Johan
J
Brain Inflammation and Immunity Group, Department of Medical Biochemistry and Immunology, University of Wales College of Medicine, Cardiff, UK. van_beek@hotmail.com
Elward
Kristina
K
Gasque
Philippe
P
D000544:Alzheimer Disease / Q000276:immunology; D000818:Animals; D001921:Brain / Q000276:immunology*; D002545:Brain Ischemia / Q000276:immunology; D003167:Complement Activation / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D008954:Models, Biological; D009410:Nerve Degeneration / Q000276:immunology*; D009474:Neurons / Q000276:immunology / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010587:Phagocytosis / Q000276:immunology
D018696:Neuroprotective Agents