Salivating for Knowledge Potential Pharmacological Agents in Tick Saliva 英文参考文献.docVIP

Research in Translation Salivating for Knowledge: Potential Pharmacological Agents in Tick Saliva Joppe W. R. Hovius , Marcel Levi, Erol Fikrig * T he incidence of tick-borne diseases has drastically increased over the past few years [1,2], resulting in a marked increase in research on tick–host–pathogen Five Key Papers in the Field that counteract coagulation, enhance ?brinolysis, and inhibit platelet aggregation [7]. Traditional anticoagulant agents such as unfractionated heparin and vitamin K antagonists (e.g., warfarin) have a narrow therapeutic index, requiring frequent monitoring and dose adjustments [7]. Tick saliva presents a possible source of novel, and ideally more easily used, anticoagulant agents (Figure 1) [7]. Factor Xa inhibitors. Saliva from the soft tick Ornithodoros moubata contains a serine protease inhibitor of FXa—tick anticoagulant peptide (TAP). TAP is a Hepburn et al., 2007 [40] After identi?cation of a speci?c activated C5 inhibitor, OMCI, the authors showed how this protein can be used in an experimental animal model for myasthenia gravis. Paveglio et al., 2007 [50] Showed that a T cell inhibitor from tick saliva, Salp15, is able to prevent the development of pathological features in an animal model for atopic asthma. Labuda et al., 2006 [55] Showed that an anti-tick vaccine, directed against the 64TRP cement protein in tick saliva, prevented lethal infection of mice with the tick-borne encephalitis virus, indicating that anti-tick vaccines could be used to combat tick-borne pathogens. Ramamoorthi et al., 2005 [5] Showed that B. burgdorferi, the causative agent of Lyme disease, uses a protein in tick saliva, Salp15, to establish an infection in the mammalian host, underscoring the complex tick–host–pathogen interactions that are involved in the development of Lyme disease. interactions. As a result, the knowledge on molecules present in tick saliva and their function has signi?cantly expanded [3,4]. Ticks are obligate hematophagous ectop