gasdermin A2 Activators

Gasdermin A2 activators encompass a variety of chemical compounds that facilitate the functional activity of gasdermin A2 through different biochemical and cellular mechanisms. Dimethyl sulfoxide (DMSO), for example, is a compound known to increase cellular membrane permeability, thus enhancing the intracellular delivery of molecules that can directly activate gasdermin A2. This activation can lead to oligomerization and pore formation, which are key steps in the execution of pyroptosis, a form of programmed cell death mediated by gasdermin A2. Likewise, nigericin, an ionophore that disrupts potassium ion gradients, can indirectly promote the activation of gasdermin A2 by triggering the NLRP3 inflammasome pathway. This cascade results in the cleavage of gasdermin A2, enabling its pore-forming action and facilitating the inflammatory response. Similarly, Calcium ionophore A23187 raises intracellular calcium levels, which can stimulate the assembly and activation of the inflammasome, ultimately leading to gasdermin A2 activation.

Further contributing to the diversity of gasdermin A2 activators are compounds such as oligomycin, which inhibits ATP synthase, thereby reducing ATP levels and potentially activating inflammasomes. This can indirectly enhance the activation of gasdermin A2, promoting its role in pyroptosis. On the other hand, extracellular ATP itself serves as a signaling molecule that can bind to purinergic receptors and activate the inflammasome, resulting in the activation of gasdermin A2 and amplifying its pro-inflammatory functions. Ionomycin, another calcium ionophore, functions similarly to A23187 by increasing intracellular calcium levels and indirectly facilitating gasdermin A2 activation through inflammasome stimulation.