Abstract
The cGAS-STING signalling pathway has emerged as a key mediator of inflammation in the settings of infection, cellular stress and tissue damage. Underlying this broad involvement of the cGAS-STING pathway is its capacity to sense and regulate the cellular response towards microbial and host-derived DNAs, which serve as ubiquitous danger-associated molecules. Insights into the structural and molecular biology of the cGAS-STING pathway have enabled the development of selective small-molecule inhibitors with the potential to target the cGAS-STING axis in a number of inflammatory diseases in humans. Here, we outline the principal elements of the cGAS-STING signalling cascade and discuss the general mechanisms underlying the association of cGAS-STING activity with various autoinflammatory, autoimmune and degenerative diseases. Finally, we outline the chemical nature of recently developed cGAS and STING antagonists and summarize their potential clinical applications.
© 2021. Springer Nature Limited.
Publication types
- Research Support, Non-U.S. Gov't
- Review
MeSH terms
- Adaptor Proteins, Signal Transducing / antagonists & inhibitors*
- Adaptor Proteins, Signal Transducing / genetics
- Adaptor Proteins, Signal Transducing / immunology
- Animals
- Autophagy
- Cell Death
- Cell Proliferation
- DNA, Mitochondrial / genetics
- DNA, Mitochondrial / metabolism
- Enzyme Inhibitors / chemistry
- Enzyme Inhibitors / therapeutic use
- Gain of Function Mutation
- Humans
- Inflammation / immunology
- Inflammation / metabolism
- Inflammation / therapy*
- Inflammation Mediators / antagonists & inhibitors
- Inflammation Mediators / immunology
- Inflammation Mediators / metabolism
- Membrane Proteins / antagonists & inhibitors*
- Membrane Proteins / genetics
- Membrane Proteins / immunology
- Models, Biological
- Models, Molecular
- Nucleotides, Cyclic / immunology
- Nucleotides, Cyclic / metabolism
- Nucleotidyltransferases / antagonists & inhibitors*
- Nucleotidyltransferases / genetics
- Nucleotidyltransferases / immunology
- Signal Transduction / drug effects
- Signal Transduction / genetics
- Signal Transduction / immunology
Substances
- Adaptor Proteins, Signal Transducing
- DNA, Mitochondrial
- Enzyme Inhibitors
- Inflammation Mediators
- Membrane Proteins
- Nucleotides, Cyclic
- cyclic guanosine monophosphate-adenosine monophosphate
- Nucleotidyltransferases