the behavioral phenotype of HD in female mice. Results of this study will indicate whether E2 may protect female HD mice from striatal AA loss, normalize cortical neuronal activity and improve the behavioral phenotype associated with HD. Furthermore, results will suggest whether E2 effects on GLU transmission contribute to sex differences observed in HD mice. HD affects -30,000 people in the United States and -150,000 more are at risk for inheriting the gene. If E2 is neuroprotective in HD models, it may be a suitable therapy, particularly for women with HD. Furthermore, evaluation of the role of E2 in regulating motor circuits in the brain will provide a better understanding of how this hormone regulates normal and pathological motor control. This is particularly important because more than 40 million U.S. citizens are affected by movement disorders. E2 likely plays a critical role in motor function and neuroprotection and may represent a therapy for movement disorders and neurodegenerative conditions that is currently not well investigated. [unreadable] [unreadable] [unreadable] [unreadable]

Project Summary/Abstract Reversible protein lysine acetylation is a fundamental posttranslational modification observed in histone and non-histone proteins. Lysine acetylation can alter protein-protein and protein-DNA interactions, protein stability, and enzyme activation/deactivation. Among the major regulators of lysine acetylation is the histone deacetylase (HDAC) family. Of the 18 known human HDACs, 11 are metal-dependent hydrolases related to the acetylpolyamine amidohydrolases (APAHs). The HDACs contribute to the regulation of gene expression and many other critical cellular processes. Notably, abnormal lysine acetylation is observed in multiple human disorders, including cancer; thus HDACs are a validated drug target. Despite their critical biological functions and clinical roles as drug targets, little is known about the molecular basis for HDAC substrate specificity and inhibition. This is particularly the case fo