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International Rett Syndrome Foundation awards $2M for cutting-edge Rett syndrome research
Date:10/1/2009

mine the impact of MeCP2 loss of function by selectively knocking-out MeCP2 function in a specific population of neurons followed by rescue of function in the same discreet populations of neurons. In Rett syndrome, the catecholaminergic system may have a disproportionate impact on the development of disease. These experiments are therefore very relevant to understanding the neurological underpinnings of the disease. In addition, given the recent reversal experiments, it is clear that MeCP2 levels within cells must be carefully regulated to avoid harmful consequences of over-expression or under-expression. The expected beneficial effects of restoring MeCP2 function in specific cell populations is of great importance for this reason and could highlight new treatment strategies for Rett syndrome.

Paul H. Patterson PhD, California Institute of Technology
Regulation of MeCP2-mediated gene expression by IkB kinase alpha

MeCP2 biology is complicated because MeCP2 has been described as both a repressor and as an activator of gene expression. Maintaining critical levels of MeCP2 appears to be required for normal brain function. However, the molecules regulating MeCP2 expression itself are poorly understood. This grant proposes to test whether a cellular signaling molecule (IKKα), is involved in regulation of MeCP2 function. IKKα is responsive to a wide range of stimuli and is implicated in other neurological diseases. Thus, understanding the link between IKKα and MeCP2 may prove to be crucial for understanding Rett syndrome neuropathology and provide a link to other neurodevelopmental disorders. Future directions include identifying other MeCP2-regulated targets that are controlled by IKKα, which will likely reveal new drug target molecules and signaling pathways related to Rett syndrome. This is a novel proposal that seeks to understand the relevance of a signaling pathway that may be controlling the activity of MeC
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Contact: Dr. Antony Horton
212-459-2608
International Rett Syndrome Foundation
Source:Eurekalert

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