THE NLRC4 INFLAMMASOME CONTRIBUTES TO BRAIN INFLAMMAGING

Abstract

Inflammation is a natural part of aging in a process known as inflammaging. Inflammaging has been associated with deleterious outcomes in the aging brain. It is believed that inflammaging precedes the onset of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. The inflammasome is an arm of the innate immune response involved in the activation of the inflammatory caspase-1 and the processing of the pro-inflammatory cytokines interleukin (IL)-1b and IL-18. We have previously shown that inflammasome contributes to the inflammatory response in the central nervous system after brain and spinal cord injury as well as stroke. In addition, we have shown that inflammasome inhibition in the aging brain results in improved cognitive outcomes. In this study we analyzed the brain of young (3 months old) and aged (18 months old) mice for the expression of inflammasome proteins. Our findings indicate that the inflammasome proteins NLRC4, caspase-1, ASC, and IL-18 are elevated in the cytoplasm of cortical lysates in aged mice when compared to young. Similarly, in the cytoplasmic fraction of hippocampal lysates in aged mice, we found an increase in NLRC4, caspase-1, caspase-11, ASC and IL-1b. Moreover, ASC is involved in the cell death mechanism of pyroptosis. Interestingly, the pyroptosome is elevated in the brain of aged mice. Taken together, our data indicate that the NLCR4 inflammasome contributes to brain inflammaging and that pyroptosis contributes to cell death in the aging brain; thus highlighting the inflammasome as a novel therapeutic target for the treatment of brain inflammaging.