J Cereb Blood Flow Metab. 2009 Jul;29(7):1251-61. Epub 2009 Apr 29.

Therapeutic neutralization of the NLRP1 inflammasome reduces the innate immune response and improves histopathology after traumatic brain injury.External

de Rivero Vaccari, J. P., Lotocki, G., Alonso, O. F., Bramlett, H. M., Dietrich, W. D., Keane, R. W.,
--- - Department of Neurological Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA.
Traumatic brain injury elicits acute inflammation that in turn exacerbates primary brain damage. A crucial part of innate immunity in the immune privileged central nervous system involves production of proinflammatory cytokines mediated by inflammasome signaling. Here, we show that the nucleotide-binding, leucine-rich repeat pyrin domain containing protein 1 (NLRP1) inflammasome consisting of NLRP1, caspase-1, caspase-11, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), the X-linked inhibitor of apoptosis protein, and pannexin 1 is expressed in neurons of the cerebral cortex. Moderate parasagittal fluid-percussion injury (FPI) induced processing of interleukin-1beta, activation of caspase-1, cleavage of X-linked inhibitor of apoptosis protein, and promoted assembly of the NLRP1 inflammasome complex. Anti-ASC neutralizing antibodies administered immediately after fluid-percussion injury to injured rats reduced caspase-1 activation, X-linked inhibitor of apoptosis protein cleavage, and processing of interleukin-1beta, resulting in a significant decrease in contusion volume. These studies show that the NLRP1 inflammasome constitutes an important component of the innate central nervous system inflammatory response after traumatic brain injury and may be a novel therapeutic target for reducing the damaging effects of posttraumatic brain inflammation.
PMID: 19401709External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
CARD ASC Link Caspase1 Co-immunoprecipitation Rat cortical lysate 19401709
CARD Caspase1 Link NLRP1 Co-immunoprecipitation Rat cortical lysate 19401709
PYD ASC Link NLRP1 Co-immunoprecipitation Rat cortical lysate 19401709
(Link: click this icon to show interactions only between the two corresponding DDs)