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Fig. 3 | Journal of Neuroinflammation

Fig. 3

From: Type I interferon (IFN)-inducible Absent in Melanoma 2 proteins in neuroinflammation: implications for Alzheimer’s disease

Fig. 3

The Atm-Aim2 axis in neuroinflammation and neurodegeneration. A knockdown of the AIM2 protein expression in human normal lung fibroblasts or a deficiency of the Aim2 gene in the murine bone marrow-derived macrophages activated ATM protein kinase (a member of the PI-3-kinase/DNA-PK family, which can bind to Aim2 protein), thus suggesting a role for the Aim/AIM2 protein in inhibition of the ATM protein kinase activity. A dysfunction of ATM protein kinase in microglia accumulated DNA fragments in the cytoplasm, resulting in activation of the ISD pathway and T1 IFN response (the accumulation of cytosolic DNA did not result in activation of an inflammasome and pyroptosis). The T1 IFN response, which upregulates the expression of Aim2 protein, is predicted to “prime” microglia for activation of the Aim2/AIM2 inflammasome upon sensing higher levels of cytosolic DNA (due to TBI, pyroptosis, or infections), resulting in AD-related neuroinflammation, neurotoxicity, and neurodegeneration

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