For many of the major neurodegenerative disorders alteration of protein function and cell physiology by changes in oxygen availability or the presence of damaging oxygen radicals may underlie many of the deleterious effects of these diseases. Therefore a true in-depth understanding of how the oxidative environment affects cellular responses to protective or detrimental stimuli is of great importance. At this present time, we are only now, understanding that the modes in which we perform cell and receptor signaling investigation may be biased towards a non-physiological paradigm, i.e. investigating receptor pharmacology under atmospheric oxygen tensions. We are therefore initially undertaking a painstaking analysis first of how central nervous system tissue responds, at the genomic and proteomic level, to multiple oxygen tensions. Our results from this primary study will facilitate subsequent studies to identify how transmembrane receptor-mediated signaling paradigms, one of the most important therapeutic targets, act at these various tensions. It is highly likely, as we have seen with our preliminary data, that there are wholescale reactive genomic and proteomic cellular changes in response to altered oxygen tension environments. With these complex and widespread changes it is highly likely that receptor signaling systems may be affected and thus potentially alter the efficacy of pharmacotherapeutics. Our research will aim to generate pharmacotherapeutics that will counteract these deficits and therefore maintain pharmacological efficacy in a variety of pathophysiological or aging states.
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