Research progress of TLR4 signaling pathway and its targeted drugs

The innate immune system uses pattern recognition receptors (PRRs) or other molecular receptors to recognize pathogenic microorganisms such as the invading bacteria, and prevents the spread of infection by triggering an inflammatory response, which plays a vital role in antimicrobial defense. Toll-like receptor-4 (TLR4) is the core of innate immune system in mammals and plays a key role in bacterial endotoxin-mediated inflammation. TLR4 recognizes lipopolysaccharide (LPS) on the cell wall of Gram-negative bacteria, thereby activating the TLR4 signaling pathway, releasing pro-inflammatory factors and chemokines, and inducing inflammation. Currently, drugs targeting the TLR4 signaling pathway mainly act on LPS and its receptor LPS binding protein (LBP), CD14, myeloid differentiation protein 2 (MD2), and TLR4, such as lipid A analogs and natural products as well as their derivatives, and natural and synthetic peptides and proteins, etc. They have potential therapeutic effects in the treatment of autoimmune diseases, acute and chronic inflammation, cardiovascular diseases, and neurological diseases.