The complement cascade: Yin-Yang in neuroinflammation--neuro-protection and -degeneration.
The complement cascade has long been recognized to play a key role in inflammatory and degenerative diseases. It is a 'double edged' sword as it is necessary to maintain health, yet can have adverse effects when unregulated, often exacerbating disease. The contrasting effects of complement, depending on whether in a setting of health or disease, is the price paid to achieve flexibility in scope and degree of a protective response for the host from infection and injury. Loss or even decreased efficiency of critical regulatory control mechanisms can result in aggravated inflammation and destruction of self-tissue. The role of the complement cascade is poorly understood in the nervous system and neurological disorders. Novel studies have demonstrated that the expression of complement proteins in brain varies in different cell types and the effects of complement activation in various disease settings appear to differ. Understanding the functioning of this cascade is essential, as it has therapeutic implications. In this review, we will attempt to provide insight into how this complex cascade functions and to identify potential strategic targets for therapeutic intervention in chronic diseases as well as acute injury in the CNS.
Alexander
Jessy John
JJ
Department of Medicine, University of Chicago, Chicago, Illinois, USA. jalexand@medicine.bsd.uchicago.edu
Anderson
Aileen Judith
AJ
Barnum
Scott Robert
SR
Stevens
Beth
B
Tenner
Andrea Joan
AJ
D003167:Complement Activation / Q000502:physiology; D003165:Complement System Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008954:Models, Biological; D009422:Nervous System Diseases / Q000378:metabolism / Q000503:physiopathology*; D016709:Yin-Yang
D003165:Complement System Proteins
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