CXCR4/CXCL12 axis: "old" pathway as "novel" target for anti-inflammatory drug discovery
- PMID: 38178560
- DOI: 10.1002/med.22011
CXCR4/CXCL12 axis: "old" pathway as "novel" target for anti-inflammatory drug discovery
Abstract
Inflammation is the body's defense response to exogenous or endogenous stimuli, involving complex regulatory mechanisms. Discovering anti-inflammatory drugs with both effectiveness and long-term use safety is still the direction of researchers' efforts. The inflammatory pathway was initially identified to be involved in tumor metastasis and HIV infection. However, research in recent years has proved that the CXC chemokine receptor type 4 (CXCR4)/CXC motif chemokine ligand 12 (CXCL12) axis plays a critical role in the upstream of the inflammatory pathway due to its chemotaxis to inflammatory cells. Blocking the chemotaxis of inflammatory cells by CXCL12 at the inflammatory site may block and alleviate the inflammatory response. Therefore, developing CXCR4 antagonists has become a novel strategy for anti-inflammatory therapy. This review aimed to systematically summarize and analyze the mechanisms of action of the CXCR4/CXCL12 axis in more than 20 inflammatory diseases, highlighting its crucial role in inflammation. Additionally, the anti-inflammatory activities of CXCR4 antagonists were discussed. The findings might help generate new perspectives for developing anti-inflammatory drugs targeting the CXCR4/CXCL12 axis.
Keywords: CXCL12; CXCR4; chemokines; drug discovery; inflammatory disease.
© 2024 Wiley Periodicals LLC.
References
REFERENCES
-
- Martin E, Delarasse C. Complex role of chemokine mediators in animal models of Alzheimer's disease. Biomedical Journal. 2018;41(1):34‐40.
-
- Stahl RAK. Potential role of chemokines in human renal disease. Am J Kidney Dis. 1997;30(3):xlix‐li.
-
- Sokol CL, Luster AD. The chemokine system in innate immunity. Cold Spring Harbor Perspect Biol. 2015;7(5):a016303.
-
- Proudfoot AEI, Power CA, Wells TNC. The strategy of blocking the chemokine system to combat disease. Immunol Rev. 2000;177:246‐256.
-
- Viola A, Luster AD. Chemokines and their receptors: drug targets in immunity and inflammation. Annu Rev Pharmacol Toxicol. 2008;48:171‐197.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical