Inflammasome signaling at the heart of central nervous system pathology.
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.
Chakraborty
Swarupa
S
National Brain Research Centre, Manesar, Haryana, India.
Kaushik
Deepak Kumar
DK
Gupta
Malvika
M
Basu
Anirban
A
D000818:Animals; D002493:Central Nervous System Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007107:Immune System / Q000502:physiology; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D046912:Multiprotein Complexes