The goal of this project is to study the role of the nuclear receptor LXR (Liver X Receptor) in neuro-inflammation and neuro-degeneration. Nuclear receptors are ligand-dependent transcription factors capable of activating or repressing gene expression. Recent studies performed by the principal investigator at the University of California San Diego and by other groups have implicated LXR in the modulation of immune responses. The work proposed here will study whether LXR agonists exert effects on microglia activation, proliferation and programmed cell death in the context of neuro-inflammation.
One of the LXR target genes recently discovered by the principal investigator is an anti-apoptotic factor, AIM, specifically secreted by certain macrophage populations. W e are interested in determining whether LXR agonists promote release of this factor in the central nervous system and whether this pathway is relevant to protect neuronal cell death. By using gene expression profiling methodologies we will explore the transcriptional programs that are regulated by LXR in the context of neuro-inflammation. In vivo experiments in animal models of neuro-inflammation will provide an insight of whether LXR agonists may be used for therapeutic intervention of neuro-degenerative disorders.
Fields of science
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