George M. O'Keefe

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Alzheimer's disease (AD) is a progressive dementing neurologic illness, and the most frequent cause of dementia in the elderly. Neuritic plaques are one of the main neuropathological findings in AD, and the major protein component is the beta-amyloid protein (A beta). Another striking feature of neuritic plaques is the presence of activated microglia,(More)
The discovery of the class II transactivator (CIITA) transcription factor, and its IFN-gamma-activated promoter (promoter IV), have provided new opportunities to understand the molecular mechanisms of IFN-gamma-induced class II MHC expression. Here, we investigated the molecular regulation of IFN-gamma-induced murine CIITA promoter IV activity in(More)
Microglia are the resident macrophages of the brain, and when activated, have functions including cytokine production, phagocytosis and antigen presentation. The class II MHC genes encode proteins that present antigenic peptides to helper T cells, leading to T cell activation and the development of an antigen-specific immune response. Class II MHC gene(More)
CD40 is a type I membrane-bound molecule belonging to the TNFR superfamily that is expressed on various immune cells including macrophages and microglia. The aberrant expression of CD40 is involved in the initiation and maintenance of various human diseases including multiple sclerosis, arthritis, atherosclerosis, and Alzheimer's disease. Inhibition of CD40(More)
Multiple kinase events, involving both tyrosine (tyr) kinase and serine/threonine (ser/thr) kinase activity, are required for IFN-gamma-induced class II MHC mRNA and protein expression in primary rat astrocytes. In this study, we examined the necessity of ser/thr and tyr kinase activity for IFN-gamma-induced stimulation of class II MHC gene expression in(More)
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