Absent in melanoma 2 (AIM2) inflammasome (AIM2)

The Absent in melanoma 2 (AIM2) inflammasome is a critical component of the innate immune system that functions as a cytosolic sensor for double-stranded DNA (dsDNA) (Hornung et al., 2009, Nature). It is a multi-protein complex consisting of the AIM2 protein, the adapter protein ASC, and the effector protease caspase-1. Upon detecting dsDNA from pathogens or damaged host cells, the AIM2 HIN-200 domain binds the DNA, while its pyrin domain (PYD) interacts with ASC to initiate inflammasome assembly (Fernandes-Alnemri et al., 2009, Nature). This assembly leads to the activation of caspase-1, which processes the pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18) into their active forms and triggers pyroptosis (Rathinam et al., 2010, Nature). While essential for defense against DNA-containing bacteria and viruses, chronic or inappropriate activation of the AIM2 inflammasome is linked to autoimmune and inflammatory diseases such as systemic lupus erythematosus and psoriasis (Dombrowski et al., 2011, Nature Medicine). In the context of oncology, AIM2 exhibits a dual role, acting as a tumor suppressor in colorectal cancer but potentially promoting progression in other malignancies (Choubey, 2016, Journal of Interferon & Cytokine Research). Therapeutic strategies currently under investigation include small molecules and suppressive oligonucleotides designed to inhibit DNA binding or complex formation to alleviate pathological inflammation (Kaminski et al., 2013, Science Signaling).

Other names

Absent in melanoma 2IFI210PYHIN4Interferon-inducible protein 210

Inhibition of the HIN-200 domain's interaction with cytosolic double-stranded DNA or disruption of the pyrin domain (PYD) mediated recruitment of the ASC adapter protein, thereby preventing the assembly of the inflammasome complex and the subsequent activation of caspase-1 (Hornung et al., 2009, Nature; Lu et al., 2015, Nature Immunology).