Roles of the complement system in human neurodegenerative disorders: pro-inflammatory and tissue remodeling activities.
Complement is an important component of the innate immune response with the capacity to recognize and clear infectious challenges that invade the CNS through a damaged blood brain barrier. For instance, the membrane attack complex is involved in cytotoxic and cytolytic activities while other smaller fragments lead to cell activation (chemotaxis) and phagocytosis of the intruders. It is noteworthy that there is a growing body of evidence that uncontrolled complement biosynthesis and activation in the CNS can contribute to exacerbate the neuronal loss in several neurodegenerative disorders. We provide here an insightful review of the double-edged sword activities of the local innate complement system in the CNS and discuss further the potential therapeutic avenues of delivering complement inhibitors to control brain inflammation.
Gasque
Philippe
P
Department of Medical Biochemistry, University of Wales College of Medicine, Cardiff, UK. Gasque@cardiff.ac.uk
Neal
Jim W
JW
Singhrao
Sim K
SK
McGreal
Eamon P
EP
Dean
Yann D
YD
Van
Beek Johan
BJ
Morgan
B Paul
BP
D000818:Animals; D003167:Complement Activation; D003169:Complement Inactivator Proteins / Q000494:pharmacology / Q000627:therapeutic use; D003165:Complement System Proteins / Q000502:physiology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007249:Inflammation; D023421:Models, Animal; D018448:Models, Immunological; D009419:Nerve Tissue Proteins / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009895:Opsonin Proteins / Q000502:physiology; D010587:Phagocytosis; D011951:Receptors, Complement / Q000502:physiology
D003169:Complement Inactivator Proteins; D009419:Nerve Tissue Proteins; D009895:Opsonin Proteins; D011951:Receptors, Complement; D003165:Complement System Proteins