Inflammasome signaling at the heart of central nervous system pathology.
J Neurosci Res
; 88(8): 1615-31, 2010 Jun.
Article
in En
| MEDLINE
| ID: mdl-20127816
ABSTRACT
Neuroinflammation is a complex innate response of neural tissue against harmful effects of diverse stimuli viz., pathogens, damaged cells and irritants within the Central Nervous System (CNS). Studies show that multiple inflammatory mediators including cytokines, chemokines and prostaglandins are elevated in the Cerebrospinal Fluid (CSF) and in post-mortem brain tissues of patients with history of neuroinflammatory conditions as well as neurodegenerative disorders like Alzheimer's disease, Parkinson's disease and Multiple Sclerosis. The innate immunity mediators in the brain, namely microglia and astrocytes, express certain Pattern Recognition Receptors (PRRs), which are always on 'high-alert' for pathogens or other inflammatory triggers and participate in the assembly and activation of the inflammasome. The inflammasome orchestrates the activation of the precursors of proinflammatory caspases, which in turn, cleave the precursor forms of interleukin-1beta, IL-18 and IL-33 into their active forms; the secretion of which leads to a potent inflammatory response, and/or influences the release of toxins from glial and endothelial cells. Altered expression of inflammasome mediators can either promote or inhibit neurodegenerative processes. Therefore, modulating the inflammasome machinery seems a better combat strategy than summarily suppressing all inflammation in most neuroinflammatory conditions. In the current review we have surveyed the identified triggers and pathways of inflammasome activation and the following events which ultimately accomplish the innate inflammatory response in the CNS, with a goal to provide an analytical insight into disease pathogenesis that might provide cues for devising novel therapeutic strategies.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Central Nervous System Diseases
/
Multiprotein Complexes
/
Inflammation
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
J Neurosci Res
Year:
2010
Document type:
Article
Affiliation country:
India