Alzheimer's Disease Chemical Causes and Prevention

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IBI SEMINAR SERIES
Alzheimer's Disease - Chemical Causes and
Prevention Arvi Rauk Professor Department of
Chemistry, University of Calgary Tuesday
January 27, 2009 1200 Noon Biological Sciences
211 University of Calgary Host Dennis Salahub
Abstract Alzheimers disease is a complex,
fatal, neurological disorder brought on largely
by old age, and characterized by the presence of
extracellular senile plaques and intracellular
fibrillary tangles. The brain is besieged by
oxidative stress, metal sequestration, membrane
damage, and blocked neuronal receptors. The
damaging agent is an oligomeric form of a 40-42
residue peptide, Ab. For the last decade, we
have investigated computationally the chemical
causes of the neurotoxicity of Ab. Our initial
working hypothesis, Radical Theory of
Alzheimers Disease, rationalized all of the
chemistry of Alzheimers disease as it was
understood a decade ago. While the model has
evolved over time, the radical chemistry required
for the hypothesis has been readily amenable to
computational investigations, from the initiating
copper-peptide complexes, to methionine oxidation
and glycyl backbone radical generation, to the
first steps of lipid peroxidation by which
neuronal and mitochondrial cell membranes are
destroyed. We have also examined by molecular
dynamics simulations the structures of Ab and
polyunsaturated membranes, and the energetics of
peptide-peptide interactions that mediate the
self-aggregation of Ab into neurotoxic oligomers.
This talk will highlight some of this work and
point to promising directions for the development
of drugs that may prevent Alzheimers disease, or
at least delay its onset.
Pizza and pop will be provided