TABLE 2.
STING activity in chronic CNS pathologies.
| Pathology | Rodent models | Human | Genetic/pharmacological intervention | References |
| Parkinson’s disease (PD) | STING pathway implicated in the onset of neuroinflammation, neurodegeneration and motor deficits in Parkin–/– mice | N/A | Genetic deletion of STING attenuates the loss of dopaminergic neurons and motor deficits seen in Parkin–/– mice | Sliter et al., 2018 |
| Ataxia telangiectasia (AT) | STING drives type-I IFN induction in ATM–/– mice | N/A | Genetic deletion of STING reduced type-I IFN response caused by loss of ATM gene | Hartlova et al., 2015 |
| Huntington’s disease (HD) | Increased cGAS, p-TBK1 and p-STING expression found in HdhQ111/Q111 mice | Increased cGAS protein expression found in HD striatal neurons | N/A | Sharma et al., 2020 |
| Multiple Sclerosis (MS) | STING-induced type-I IFN production attenuates EAE pathology Mice lacking functional STING display attenuated EAE development | cGAS and STING gene expression is downregulated in relapsed MS patients | Use of STING agonist c-di-GMP delayed disease onset and severity in EAE mouse model Activating STING using antiviral therapeutic ganciclovir was able to attenuate disease progression in EAE mice | Lemos et al., 2014; Mathur et al., 2017; Masanneck et al., 2020 |
| Systemic lupus erythematosus (SLE) | Loss of STING accelerates mortality and disease progression in Lupus prone mice (MRL-Faslpr) | ISG inducing activity of sera derived from SLE patients is STING dependent | N/A | Sharma et al., 2015; Kato et al., 2018 |
| Amyotrophic lateral sclerosis (ALS) | Increased cGAS and cGAMP detected in the spinal cords of Prp-TDP-43Tg/+ mice Genetic deletion of STING in Prp-TDP-43Tg/+ mice increased average lifespan by 40% | Elevated levels of cGAMP detected in the spinal cords of ALS patients | Administration of small-molecule STING inhibitor H-151 reduced cortical and spinal cord proinflammatory cytokine gene expression and reduced neurodegeneration in ALS mice. Death of ALS patient iPSC -derived motor neurons was prevented following H-151 administration | Yu et al., 2020 |