Bioloical role of Toll.docVIP

iologiBcal role of Toll-like receptor-4 in the brain The Toll-like receptors (TLRs) are a family of microbe-sensing receptors that play a central role in the regulation of the host immune system.?TLR4?has been described in the brain and seems to regulate some physiological processes, such as?neurogenesis. TLR4 has also been reported to play a role during neurodegenerative disorders, including?Alzheimers disease,?amyotrophic lateral sclerosis,?multiple sclerosisand?Parkinsons disease. This review is focused on reports concerning recent insights into the role and activation mechanisms of TLR4 in the brain, in pathological and physiological conditions, as well as the therapeutic benefit that could derive from?TLR4?modulation. TLR4 在大脑中的生物角色 TLRs 是细菌传感器家族的一员，在宿主免疫系统中发挥着核心作用。TLE4 据称在大脑中似乎调节一些生理过程，如神经再生。TLR4 也被报道在神经退行性疾病中发挥作用，包括 1. Introduction Mammalian Toll-like receptors (TLRs) were initially discovered because of their sequence similarities to?Tollinvolved in?Drosophila?dorsoventral?embryonic development and antifungal immunity (?Nüsslein-Volhard and Wieschaus, 1980,?Steward et al., 1984?and?Lemaitre et al., 1996). In 1997, Medzhitov et al. cloned a human homolog of the?Drosophila?Toll protein, now known as?TLR4, and showed that Toll signaling was able to stimulate adaptive immune responses (?Medzhitov et al., 1997). Shortly after, the Toll gene was discovered to be an important component for the detection of microbes in?Drosophila melanogaster, as well as demonstrations that TLR4 mediates the inflammatory response to?lipopolysaccharide?(LPS) in mice (Poltorak et al., 1998?and?Poltorak et al., 2000). This led to the identification of the target molecule of LPS on the cellular surface of macrophages. These discoveries substantially extended the knowledge of pathogen-mediated intra-cellular?signal transduction, and were crucial for understanding the mechanisms that govern innate immunity (?Bode et al., 2012). In general, mammalian cells recognize the presence of pathoge