Year: 2014
Type: article
Abstract: We welcomed the correspondence by Dr Takahashi regarding the functions of NLRP3. In our article, 1 we had focused on interleukin-1, and, as such, we mainly discussed the inflammasome-dependent NLRP3 functions, but we fully agree with the concept that NLRP3 has inflammasome-independent functions. How important the inflammasome-independent functions of NLRP3 are in heart disease is unclear. To summarize, the NLRP3 is one of the sensors involved in the macromolecular assembly that leads to caspase-1 activation and the maturation of pro-interleukin-1, the inflammasome. As such, the inflammasome can form in absence of NLRP3 when another sensor is activated. When activated, NLRP3 recruits the adaptor protein ASC, which is the main scaffold protein of the inflammasome. Activation of the inflammasome leads to caspase-1-dependent cell death known as pyroptosis or pyronecrosis. 2 A study in leukocytes carrying a mutant form of constitutively active NLRP3 showed that the induction of cell death could not be rescued by caspase-1 inhibition, yet it was dependent on the presence of ASC, demonstrating that NLRP3/ASC can be involved in modalities of cell death independent of caspase-1. oreover, studies in genetically modified mice lacking NLRP3 or ASC showed that NLRP3 can promote cell death also independent of ASC, 4 a form of cell death independent of caspase-1 that appears to have morphological characteristics common to oncosis and apoptosis. Caspase-1-dependent cell death, however, appears to be very important in experimental acute myocardial infarction and heart failure, 2,5,6 and whether NLRP3-mediated/caspase-1-independent cell death contributes to the injury or not needs to be further investigated.
Source: Circulation
Institution: Virginia Commonwealth University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2037333404