The emerging roles of absent in melanoma 2 (AIM2) inflammasome in central nervous system disorders

As a double-stranded DNA (dsDNA) sensor, the PYHIN family member absent in melanoma 2 (AIM2) is an essential component of the inflammasome families. Activation of AIM2 by dsDNA leads to the assembly of cytosolic multimolecular complexes termed the AIM2 inflammasome, resulting in activation of caspase-1, the maturation and secretion of pro-inflammatory cytokines interleukin (IL)-1β and IL-18, and pyroptosis. Multiple central nervous system (CNS) diseases are accompanied by immune responses and inflammatory cascade. As the resident macrophage cells, microglia cells act as the first and main form of active immune defense in the CNS. AIM2 is highly expressed in microglia as well as astrocytes and neurons and is essential in neurodevelopment. In this review, we highlight the recent progress on the role of AIM2 inflammasome in CNS disorders, including cerebral stroke, brain injury, neuropsychiatric disease, neurodegenerative diseases, and glioblastoma. •We reviewed the recent progress on the roles of AIM2 inflammasome in multiple CNS disorders.•We discussed the therapeutic potential and challenges by targeting AIM2 for CNS disorders.•We summarized the natural beneficial ingredients that could inhibit the activation of AIM2 inflammasome.