2010 Archived Content
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Recommended Short Courses*
Monday, June 14
9:00 am – 12:00 pm(SC1) Reactive Metabolites in Drug Discovery and Development-A Critical Examination of the Issues
2:00 pm – 5:00 pm(SC5) Dealing with the Blood-Brain Barrier
*Separate Registration Required.
WEDNESDAY, JUNE 16
12:30 pm Registration
1:55 Chairperson's Opening Remarks
Timothy A. Esbenshade, Senior Group Leader, Associate Fellow, Neuroscience Research, Abbott Laboratories
2:00 Recreating Full AD-like Disease Progression in Mouse Models
Carol A. Colton, Ph.D., Professor, Neurology, Duke University
Few, if any, mouse models recreate human AD pathology and lack the characteristic tau pathology and neuronal loss observed in AD. Taking advantage of the dual role of nitric oxide (NO) in innate immunity and in redox balance (two key factors in chronic neurodegeneration), we generated novel mouse models that show complete AD-like disease progression including amyloid deposition, hyperphosphorylated and aggregated normal mouse tau protein redistributed to neuronal soma, neuronal loss and robust behavioral deficits. Innate immune gene profiles also closely mimic AD. The observed disease progression suggests that species-specific differences between NOS2 in humans and mice may contribute to differences in the “sensitivity” of the brain to Aβ-mediated damage and imply a critical role for NO in AD pathogenesis.
2:30 Dysregulation of Histone Acetylation in Alzheimer's Disease
Ottavio Arancio, M.D., Ph.D., Associate Professor, Department of Pathology and Cell Biology & The Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University
Epigenetic mechanisms such as post-translational histone modifications are increasingly recognized for their contribution to gene activation and silencing in the brain. We will present data showing that an Alzheimer’s disease (AD) mouse model has a reduction in histone acetylation levels during associative memory formation. Drugs up-regulating histone acetylation rescue both the synaptic and memory phenotype in the AD mouse.
3:00 Selected Poster Presentation
Inhibition of APP Processing with HPP854, a Novel, Selective, Orally Active Inhibitor of Beta Amyloid Cleavage Enzyme (BACE), Results in Therapeutic Benefit in an Animal Model of Alzheimer’s Disease
Matthew Kostura, Ph.D., Vice President, Biology, Trans Tech Pharma
3:30 Networking Refreshment Break, Poster and Exhibit Viewing
4:30 Animal Models of Neurological Disorders in Drug Discovery Research
Jean-Cosme Dodart, Ph.D., Director, Mouse NeuroBehavior Core, Harvard NeuroDiscovery Center, Harvard Medical School
Genetically-engineered mouse (GEM) models are now widely used to support a variety of preclinical drug discovery programs, as tools for target validation, for biomarkers research or for pre-clinical proof-of-concept. In this overview, examples of GEM models of Alzheimer’s and Parkinson’s diseases will be presented, and their application to drug discovery research as well as their translational value will be discussed.
5:00 Contributions of APP Intracellular Domain (AICD) to Alzheimer’s Disease: The Evidence and the Mechanism
Sanjay W. Pimplikar, Ph.D., Assistant Staff, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation
It is becoming clear that non-amyloid-BETA factors contribute significantly to AD pathogenesis and are potential drug targets. We earlier showed that APP IntraCellular Domain (AICD) causes AD-like pathologies in mice and its levels are increased in human AD brains. Here, we will present the mechanism of AICD-induced pathogenesis and discuss how this pathway suggests unexplored non-amyloid targets for therapeutic interventions.
5:30 KEYNOTE ADDRESS
Targeting Neurodegeneration: Genes, Biomarkers and Therapies
David S. Bredt, M.D., Ph.D., Vice President, Neuroscience Discovery and Clinical Investigation, Lilly Research Laboratories, Eli Lilly
6:00 End of Day
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