Versatility of the complement system in neuroinflammation, neurodegeneration and brain homeostasis

作者：Franca Orsini, Daiana De Blasio, Rosalia Zangari, Elisa Roncati Zanier, Maria Grazia De Simoni · 发表于：Frontiers in Cellular Neuroscience · 年份：2014 · DOI：10.3389/fncel.2014.00380 · 被引用次数：207 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Complement system in diseases、Neonatal and fetal brain pathology

The immune response after brain injury is highly complex and involves both local and systemic events at the cellular and molecular level. It is associated to a dramatic over-activation of enzyme systems, the expression of proinflammatory genes and the activation/recruitment of immune cells. The complement system represents a powerful component of the innate immunity and is highly involved in the inflammatory response. Complement components are synthesized predominantly by the liver and circulate in the bloodstream primed for activation. Moreover, brain cells can produce complement proteins and receptors. After acute brain injury, the rapid and uncontrolled activation of the complement leads to massive release of inflammatory anaphylatoxins, recruitment of cells to the injury site, phagocytosis and induction of blood brain barrier (BBB) damage. Brain endothelial cells are particularly susceptible to complement-mediated effects, since they are exposed to both circulating and locally synthesized complement proteins. Conversely, during neurodegenerative disorders, complement factors play distinct roles depending on the stage and degree of neuropathology. In addition to the deleterious role of the complement, increasing evidence suggest that it may also play a role in normal nervous system development (wiring the brain) and adulthood (either maintaining brain homeostasis or supporting regeneration after brain injury). This article represents a compendium of the current knowledge o...