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Recent studies have implicated the nuclear receptor co- repressor N-CoR in mediating the suppressive effects of glucocorticoids on expression of pro-inflammatory genes in macrophages and osteoblasts. N-CoR is also able to bind to the glucocorticoid response element to inhibit transcriptional activation. The aim of this proposal is to determine if glucocorticoids exert similar neuroprotective effects through inhibition of N-CoR function. Recently, we demonstrated that glucocorticoids enhance the stability and reduce the transcriptional activity of N-CoR in neurons. Furthermore, these actions were mediated through a direct interaction with N-CoR. Given the broad importance of N-CoR in mediating glucocorticoid responses, and the fact that glucocorticoids are important regulators of neuronal function, we hypothesize that glucocorticoids regulate neuronal function by controlling the cellular levels and nuclear transactivation activity of N-CoR. We will investigate this hypothesis using N-CoR knockout mice and primary neuronal cultures derived from these mice. Furthermore, we will explore the molecular mechanism by which glucocorticoids control N-CoR stability and transcriptional activity. Collectively, these studies will define the role of N-CoR in mediating the neuroprotective effects of glucocorticoids, and will provide a foundation for future studies to define the molecular basis by which N-CoR is regulated. Such studies may ultimately lead to novel approaches for the development of therapeutics for the treatment of neuropsychiatric disorders.Q: how ThGCube Crack A compact and clean desktop program that can help you keep your eyes from getting tired. A great window management tool that provides an easy to use solution to window management. A very good starting point to customize windows according to your preferences. 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