Activation of Complement in the Central Nervous System

Roles in Neurodegeneration and Neuroprotection

Authors

  • JOHAN Van BEEK,

    Corresponding author
    1. Brain Inflammation and Immunity Group (BIIG), Department of Medical Biochemistry and Immunology, University of Wales College of Medicine, Cardiff, UK
      Address for correspondence: Dr. Johan van Beek, Department of Medical Biochemistry and Immunology, Tenovus Building 3rd Floor, University of Wales College of Medicine, Cardiff CF 14 4XX, United Kingdom. Voice: +44 2920 745254; fax: +44 2920 744305. van_beek@hotmail.com
    Search for more papers by this author
  • KRISTINA ELWARD,

    1. Brain Inflammation and Immunity Group (BIIG), Department of Medical Biochemistry and Immunology, University of Wales College of Medicine, Cardiff, UK
    Search for more papers by this author
  • PHILIPPE GASQUE

    1. Brain Inflammation and Immunity Group (BIIG), Department of Medical Biochemistry and Immunology, University of Wales College of Medicine, Cardiff, UK
    Search for more papers by this author

Address for correspondence: Dr. Johan van Beek, Department of Medical Biochemistry and Immunology, Tenovus Building 3rd Floor, University of Wales College of Medicine, Cardiff CF 14 4XX, United Kingdom. Voice: +44 2920 745254; fax: +44 2920 744305. van_beek@hotmail.com

Abstract

Abstract: 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.

Ancillary