STING signaling in neurological disease
| Neurological disease . | Type of evidence for STING involvement . | Mode of STING activation . | Role of STING signaling . |
|---|---|---|---|
| ALS and FTD | Genetic, pharmacological inhibitor | Ligand (mtDNA, e.g., TDP-43), trafficking (e.g., C9ORF72) | Genetic deficiency or inhibition of STING signaling in a mouse model protects against disease progression; STING inhibitor reduces IFN expression in patient cells (Yu et al., 2020; McCauley et al., 2020) |
| PD | Genetic, expression | Ligand (mtDNA) | Protection from development of motor deficits in a STING-deficient mouse model; STING protein expression in substantia nigra correlates with α-synuclein deposition in patients (Hinkle et al., 2022; Sliter et al., 2018) |
| NPC | Genetic | Trafficking | STING-deficient mouse model displays improved motor function (Chu et al., 2021) |
| Huntington’s disease | Expression | Unknown | Elevated p-STING in a mouse model (Sharma et al., 2020) |
| Ataxia telangiectasia | Pharmacological inhibitor | Ligand (likely gDNA from DNA damage) | Pharmacological inhibition of STING reduces senescence phenotypes and inflammation in brain organoids model (Aguado et al., 2021) |
| Traumatic brain injury | Genetic, expression | Unknown | Decreased levels of pro-inflammatory cytokines in a STING-deficient mouse model; STING expression and activity upregulated in late trauma human brain samples and a mouse model (Abdullah et al., 2018; Barrett et al., 2020; Sen et al., 2020) |
| Ischemic brain injury and stroke | Pharmacological inhibitor | Unknown | Pharmacological inhibition of STING reduces brain infarction, neuronal injury, and cognitive deficits in a mouse model (Kong et al., 2022) |
| Subarachnoid hemorrhage | Pharmacological inhibitor | Unknown | STING inhibition improves edema, neuronal injury, inflammation, and behavioral outcome in a mouse model (Peng et al., 2020) |
| Neurological disease . | Type of evidence for STING involvement . | Mode of STING activation . | Role of STING signaling . |
|---|---|---|---|
| ALS and FTD | Genetic, pharmacological inhibitor | Ligand (mtDNA, e.g., TDP-43), trafficking (e.g., C9ORF72) | Genetic deficiency or inhibition of STING signaling in a mouse model protects against disease progression; STING inhibitor reduces IFN expression in patient cells (Yu et al., 2020; McCauley et al., 2020) |
| PD | Genetic, expression | Ligand (mtDNA) | Protection from development of motor deficits in a STING-deficient mouse model; STING protein expression in substantia nigra correlates with α-synuclein deposition in patients (Hinkle et al., 2022; Sliter et al., 2018) |
| NPC | Genetic | Trafficking | STING-deficient mouse model displays improved motor function (Chu et al., 2021) |
| Huntington’s disease | Expression | Unknown | Elevated p-STING in a mouse model (Sharma et al., 2020) |
| Ataxia telangiectasia | Pharmacological inhibitor | Ligand (likely gDNA from DNA damage) | Pharmacological inhibition of STING reduces senescence phenotypes and inflammation in brain organoids model (Aguado et al., 2021) |
| Traumatic brain injury | Genetic, expression | Unknown | Decreased levels of pro-inflammatory cytokines in a STING-deficient mouse model; STING expression and activity upregulated in late trauma human brain samples and a mouse model (Abdullah et al., 2018; Barrett et al., 2020; Sen et al., 2020) |
| Ischemic brain injury and stroke | Pharmacological inhibitor | Unknown | Pharmacological inhibition of STING reduces brain infarction, neuronal injury, and cognitive deficits in a mouse model (Kong et al., 2022) |
| Subarachnoid hemorrhage | Pharmacological inhibitor | Unknown | STING inhibition improves edema, neuronal injury, inflammation, and behavioral outcome in a mouse model (Peng et al., 2020) |