Table 2.
Human diseases related to deregulated cGAS signaling
| Disease | Possible pathogens involved | Regulatory function and effects | References |
|---|---|---|---|
| Acute pancreatitis (AP) | Unknown | cGAS loss-mediated reduction in IFN-β release exerts a protective role in AP | 196 |
| Age-dependent macular degeneration (AMD) | Mitochondrial DNA (mtDNA) | mtDNA driven cGAS activation to potentiate type I IFN signaling | 200 |
| Alcoholic liver disease (ALD) | Unknown | cGAS activation observed in both ALD mouse models and ALD patients, and cGAS activation correlates with disease severity | 225 |
| Aicardi–Goutières syndrome (AGS) | Nuclear DNA | Increased expression of type I IFNs and interferon-stimulated genes (ISG) caused by cGAS activation | 219 |
| Aujeszky’s disease | Nuclear DNA | Activation of cGAS-mediated innate immunity observed in disease to increase host resistance to viral infection | 220 |
| Alzheimer’s disease | mtDNA | mtDNA activates cGAS signaling and mitophagy via an ALDH2-dependent mechanism | 193 |
| Asthma | Cytosolic dsDNA | cGAS deletion in mouse airway ECs significantly attenuated OVA- or HDM-induced airway eosinophilic inflammation, mucus overproduction, and airway hyperresponsiveness (AHR) | 198 |
| Bloom syndrome | Unknown | Elevated ISG expression observed in peripheral blood presumably due to cGAS activation | 226 |
| Familial chilblain lupus (FCL) | Cytosolic DNA | Aberrant IFN signature and inflammasome activation observed presumably due to cGAS activation | 65,227 |
| Hutchinson–Gilford progeria syndrome | Unknown | Activation of cGAS and a robust STAT1-regulated IFN-like response | 228 |
| Huntington disease (HD) | Unknown | cGAS is activated in HD in mediating inflammatory and autophagy responses | 229 |
| Myocardial infarction (MI) | Extracellular DNA | During cardiac ischemia, cGAS serves as a pattern-recognition receptor in the sterile immune response | 202,230 |
| Parkinson’s disease | mtDNA | LRRK2 deletion in mice causes mitochondria stress leading to chronic cGAS activation to produce IFNs. | 231 |
| Systemic lupus erythematosus (SLE) | Cytosolic DNA | Caused by increased cGAS activation due to aberrant accumulation of cytosolic DNA | 65,66,195 |
| Cancer | Cytosolic DNA | Reduced expression of cGAS associated with poor patient survival in lung, brain, colorectal, and breast cancer patients and creates a tumor-prone immune microenvironment through suppressing innate immunity; on the other hand, cGAS promotes genome instability through inhibiting homologous recombination to promote lung cancer growth and 2'3'-cGAMP facilitates breast tumor metastasis in brain. | 64,68,70,207 |