Infectious agents contribute to AD and ATH Wild type mice inoculated with Enzastaurin 170364-57-5 C. pneumoniae culti vated from AD brain developed amyloid plaques. HSV 1 infection of cultured neuronal and glial cells Inhibitors,Modulators,Libraries leads to a dramatic increase in the intracellular levels of AB, and antiviral therapy blocked AB production. Infection with neuroadapted mouse hepatitis virus strain JHM was also reported to exacerbate AD like pathology in a transgenic mouse AD model. Of note, AB deposition is a common feature of brain infection with HIV in human. Conversely, immunosuppressive Toxoplasma gondii inhibited disease development in an APP Inhibitors,Modulators,Libraries AD mouse model. For ATH, diverse experiments in animal models have demonstrated that inoculated infectious agents such as C. pneumoniae persist in atherosclerotic lesions and accelerate ATH development in susceptible mice.
For example, C. pneumoniae infection increased aortic ATH in the Ldlr mouse model, although this has been disputed, and infection can stimulate cholesterol rich foam cell formation and SMC proliferation, markers of ATH. Infection Inhibitors,Modulators,Libraries of ATH mouse models with Porphyromonas gingivalis, H. pylori, or Streptococcus mutans also accelerated atherogenesis. Similar results have been obtained with viral pathogens. Virus infection of ATH prone mice promotes atherogenesis, exemplified by mouse gammaherpesvirus 68, influenza virus, and CMV. Conversely, as with AD, infection with an immunosup pressive pathogen reduced ATH lesions by 50% in infected mice. Non specific immune activation predisposes to disease Infection is not strictly required for atherogenesis.
Wright et al. reported that the profile of ATH de velopment was unaffected in Apoe mice additionally carrying the lpsd mutation that renders them unable to respond to bacterial lipopolysaccharide Inhibitors,Modulators,Libraries although LPS is only one of multiple stimulators of innate im munity. Germfree Apoe mice, that are held to be free of bacteria, viruses, and fungi, developed atherosclerosis. However, non specific immune challenge can precipitate disease. LPS injections alone can increase atherosclerotic lesion size. Vliegen et al. compared the effects of inoculation of mouse CMV with ultraviolet light treated MCMV. The inactivated virus increased atherosclerotic lesion area and T cell number in the atherosclerotic lesions, whereas only live MCMV infection increased T cell numbers in the internal organs.
Similar findings have been made in AD models. Trans mission of disease has been reported but, importantly, heating AD brain extracts to Inhibitors,Modulators,Libraries 95 C reduced but did not eliminate transmission, arguing for a non specific inflammatory effect. In support, systemic immune stimulation with the viral mimetic, poly, dur ing gestation predisposes to AD like neuropathology. Prenatally stimulated license with Pfizer animals had increased levels of AB, hyperphosphorylated Tau, and NFT formation. Lee et al.