The detection of extranuclear DNA (self or foreign) by Cyclic GMP-AMP synthase (cGAS) is crucial for human health.
cGAS triggers the production of the second messenger cyclic guanosine monophosphate (cGMP) upon binding to extranuclear DNA. This, in turn, activates the stimulator of interferon genes (STING) - producing a range of cellular responses, including the activation of interferon regulatory factor 3 (IRF3) and the release of interferons.
Collectively, this process is known as the cGAS-STING pathway. Its activation drives multiple cellular responses, including cell cycle arrest, apoptosis, and immune system activation/recruitment.
This research collection aims to explore the various mechanisms of cGAS-STING activation and its role in human health and disease.
It has been recently discovered that chromosome segregation defects activate the cGAS-STING pathway in systemic sclerosis - likely contributing to aberrant autoimmunity. Significant efforts are underway to discover specific and effective cGAS-STING inhibitors as researchers aim to blunt the cGAS-STING pathway in auto-immune disorders.
Conversely, cGAS-STING agonists may also be a valuable therapeutic. A recent study has shown that cGAS-STING activation induces IFN-ß and primes CD8+ T cells against tumor cells. In this context, cGAS-STING agonists show exciting potential for cancer immunotherapy. However, some studies have shown that the cGAS-STING pathway promotes tumorigenesis and metastasis.
These seemingly contradictory findings highlight the importance of further research into cGAS-STING signaling. This research collection will expand the basic knowledge of cGAS-STING signaling, by highlighting advancements in the development of cGAS-STING modulators and thus advancing this promising avenue of drug discovery for the treatment of auto-immune diseases and cancer.
This research collection is aimed to accommodate broad-spectrum research on the cGAS-STING pathway.
The scope of this research topic includes, but is not limited to:
1. Basic mechanisms of the cGAS-STING pathway; activation by micronuclei and DNA bridges, DNA damage, mitochondrial DNA damage, infection by pathogens, etc. and its pharmacological implication in drug discovery.
2. Crosstalk of the cGAS-STING pathway with pathways related to cell fate; autophagy and mitophagy, apoptosis, senescence, and new avenues for pharmacological intervention
3. Screening and discoveries of inhibitors of the cGAS-STING pathway and its application in auto-immune diseases.
4. cGAS-STING pathway and cancer immunotherapy, cGAS-STING pathway agonists, and possible cancer treatment options.
The detection of extranuclear DNA (self or foreign) by Cyclic GMP-AMP synthase (cGAS) is crucial for human health.
cGAS triggers the production of the second messenger cyclic guanosine monophosphate (cGMP) upon binding to extranuclear DNA. This, in turn, activates the stimulator of interferon genes (STING) - producing a range of cellular responses, including the activation of interferon regulatory factor 3 (IRF3) and the release of interferons.
Collectively, this process is known as the cGAS-STING pathway. Its activation drives multiple cellular responses, including cell cycle arrest, apoptosis, and immune system activation/recruitment.
This research collection aims to explore the various mechanisms of cGAS-STING activation and its role in human health and disease.
It has been recently discovered that chromosome segregation defects activate the cGAS-STING pathway in systemic sclerosis - likely contributing to aberrant autoimmunity. Significant efforts are underway to discover specific and effective cGAS-STING inhibitors as researchers aim to blunt the cGAS-STING pathway in auto-immune disorders.
Conversely, cGAS-STING agonists may also be a valuable therapeutic. A recent study has shown that cGAS-STING activation induces IFN-ß and primes CD8+ T cells against tumor cells. In this context, cGAS-STING agonists show exciting potential for cancer immunotherapy. However, some studies have shown that the cGAS-STING pathway promotes tumorigenesis and metastasis.
These seemingly contradictory findings highlight the importance of further research into cGAS-STING signaling. This research collection will expand the basic knowledge of cGAS-STING signaling, by highlighting advancements in the development of cGAS-STING modulators and thus advancing this promising avenue of drug discovery for the treatment of auto-immune diseases and cancer.
This research collection is aimed to accommodate broad-spectrum research on the cGAS-STING pathway.
The scope of this research topic includes, but is not limited to:
1. Basic mechanisms of the cGAS-STING pathway; activation by micronuclei and DNA bridges, DNA damage, mitochondrial DNA damage, infection by pathogens, etc. and its pharmacological implication in drug discovery.
2. Crosstalk of the cGAS-STING pathway with pathways related to cell fate; autophagy and mitophagy, apoptosis, senescence, and new avenues for pharmacological intervention
3. Screening and discoveries of inhibitors of the cGAS-STING pathway and its application in auto-immune diseases.
4. cGAS-STING pathway and cancer immunotherapy, cGAS-STING pathway agonists, and possible cancer treatment options.
