The role of STING signaling in central nervous system infection and neuroinflammatory disease.
| Title: | The role of STING signaling in central nervous system infection and neuroinflammatory disease. |
|---|---|
| Authors: | Fritsch LE; Graduate Program in Translational Biology, Medicine, and Health, Virginia Polytechnic Institute and State University, Roanoke, Virginia, USA.; Kelly C; Graduate Program in Translational Biology, Medicine, and Health, Virginia Polytechnic Institute and State University, Roanoke, Virginia, USA.; Pickrell AM; School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, USA. |
| Source: | WIREs mechanisms of disease [WIREs Mech Dis] 2023 May-Jun; Vol. 15 (3), pp. e1597. Date of Electronic Publication: 2023 Jan 12. |
| Publication Type: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review |
| Language: | English |
| Journal Info: | Publisher: John Wiley & Sons, Inc Country of Publication: United States NLM ID: 9918227353306676 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2692-9368 (Electronic) Linking ISSN: 26929368 NLM ISO Abbreviation: WIREs Mech Dis Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Hoboken, NJ] : John Wiley & Sons, Inc., [2021]- |
| MeSH Terms: | Central Nervous System Infections* ; Interferon Type I*; DNA/metabolism ; Nucleotidyltransferases/genetics ; Signal Transduction/genetics ; Humans ; Neuroinflammatory Diseases ; STING Protein |
| Abstract: | The cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) synthase-Stimulator of Interferon Genes (cGAS-STING) pathway is a critical innate immune mechanism for detecting the presence of double-stranded DNA (dsDNA) and prompting a robust immune response. Canonical cGAS-STING activation occurs when cGAS, a predominantly cytosolic pattern recognition receptor, binds microbial DNA to promote STING activation. Upon STING activation, transcription factors enter the nucleus to cause the production of Type I interferons, inflammatory cytokines whose primary function is to prime the host for viral infection by producing a number of antiviral interferon-stimulated genes. While the pathway was originally described in viral infection, more recent studies have implicated cGAS-STING signaling in a number of different contexts, including autoimmune disease, cancer, injury, and neuroinflammatory disease. This review focuses on how our understanding of the cGAS-STING pathway has evolved over time with an emphasis on the role of STING-mediated neuroinflammation and infection in the nervous system. We discuss recent findings on how STING signaling contributes to the pathology of pain, traumatic brain injury, and stroke, as well as how mitochondrial DNA may promote STING activation in common neurodegenerative diseases. We conclude by commenting on the current knowledge gaps that should be filled before STING can be an effective therapeutic target in neuroinflammatory disease. This article is categorized under: Neurological Diseases > Molecular and Cellular Physiology Infectious Diseases > Molecular and Cellular Physiology Immune System Diseases > Molecular and Cellular Physiology.; (© 2023 The Authors. WIREs Mechanisms of Disease published by Wiley Periodicals LLC.) |
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| Grant Information: | R35 GM142368 United States GM NIGMS NIH HHS; R21 AI162775 United States AI NIAID NIH HHS |
| Contributed Indexing: | Keywords: STING; brain injury; cGAS; interferons; neuroinflammation; stroke |
| Substance Nomenclature: | 9007-49-2 (DNA); 0 (Interferon Type I); EC 2.7.7.- (Nucleotidyltransferases); 0 (STING1 protein, human); 0 (STING Protein) |
| Entry Date(s): | Date Created: 20230112 Date Completed: 20230824 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10175194 |
| DOI: | 10.1002/wsbm.1597 |
| PMID: | 36632700 |
| Database: | MEDLINE |
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review