There is a dire need for the development of new therapies to address the rising incidence of neurodegenerative disease in the world's aging population. In an attempt to discover agents capable of attenuating the neuroinflammatory sequelae of these disorders, such as AIzheimer's disease (AD), we have identified a novel class of small, bioavailable compounds showing considerable promise in vitro as inhibitors of neuroinflammatory cascades, in an attempt to test the hypothesis that these compounds may be efficacious as anti-neuroinflammatory compounds in AD-relevant models of disease, we have established the amyloid beta (A-beta) infusion and amyloid precursor protein (APP) TgCRND8 models of AD. These models are highly desirable for the rapid testing of compounds in vivo, since they recapitulate the human disease process to a great degree and require only a short period of time to develop disease-relevant histological, biochemical and behavioral endpoints that may be quantified to determine the efficacy of experimental therapeutics. Furthermore, the A-beta infusion model may be used in mice carrying mutations in the mediators of certain neuroinflammatory cascades that predispose them to inflammation-related damage. These mice may then be treated with test compounds to identify and/or verify the neuroinflammatory pathways through which these agents exert their effects. ? ?
