Role of inflammation in neurodegenerative diseases.
OBJECTIVE
Inflammation is a self-defensive reaction aimed at eliminating or neutralizing injurious stimuli, and restoring tissue integrity. In neurodegenerative diseases inflammation occurs as a local response driven by microglia, in the absence of leucocyte infiltration. Like peripheral inflammation, neuroinflammation may become a harmful process, and it is now widely accepted that it may contribute to the pathogenesis of many central nervous system disorders, including chronic neurodegenerative diseases. This review addresses some of the most recent advances in our understanding of neuroinflammation.


RESULTS
The presence of activated microglia surrounding amyloid plaques and increased levels of complement elements, cytokines, chemokines and free radicals support the existence of a self-propagating toxic cycle and provide a rationale for anti-inflammatory approaches to prevent or delay neurodegeneration. Nonetheless, recent studies have provided evidence that chronic stimulation leads microglia to acquire an anti-inflammatory phenotype, characterized by activated morphology and induction of neuroprotective and immunoregulatory molecules. The causes and consequences of this atypical phenotype have just begun to be unravelled.


CONCLUSIONS
Although significant advances have been made in our knowledge of degenerative diseases, there remains controversy regarding whether neuroinflammation and microglial activation are beneficial or detrimental. Strategies aimed at both preventing and boosting microglial activation are presently under investigation, and these studies might reveal new potentially effective treatments for these neurological disorders.
Minghetti
Luisa
L
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy. luisa.minghetti@iss.it
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology*; D017628:Microglia / Q000187:drug effects / Q000502:physiology; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000503:physiopathology*
D000893:Anti-Inflammatory Agents