TLR4 (Toll-like receptor 4) is a transmembrane protein involved in the immune response, inflammation, and cytokine secretion. TLR4 activates the NF-kappa-B (NFKB) and po-Interleukin-1 beta (IL1B) pathways in the brain and is thus relevant to neuro-inflammation and pathological neurodegenerative conditions. It has been found to positively regulate the proliferation of Schwann cells in the peripheral nervous system, it is upregulated in injured nerves, and it is involved in inflammation in brain injury. TLR4 is also expressed in astrocytes and neurons as part of the immune response to bacterial lipopolysaccharide (LPS). Likewise, mutations in TLR4 lead to susceptibility to infections by gram-negative bacteria. Additionally, TLR4 is expressed on many cancer cells, where it may increase proliferative capacity and resistance to therapies. In immunohistochemistry of normal tissue, TLR4 has highest cytoplasmic positivity in immune cells, in the placenta, and in microglia and neurons in the brain. References: Archives of Internal Medicine. 162 (9): 1028–32,PMID: 11996613; Cytokine. 89: 127–135, PMID: 26854213; Sci Rep. 2018; 8: 11179, PMID: 30046125; Front Immunol. 2019 May 10;10:1000, PMID: 31134076; Front Immunol. 2019 May 10;10:1000, PMID: 31134076