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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000325-05
Application #
8552368
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2012
Total Cost
$487,755
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
Zip Code
Jasien, Joan; Daimon, Caitlin M; Maudsley, Stuart et al. (2012) Aging and bone health in individuals with developmental disabilities. Int J Endocrinol 2012:469235
Wu, Wells W; Shen, Rong-Fong; Park, Sung-Soo et al. (2012) Precursor ion exclusion for enhanced identification of plasma biomarkers. Proteomics Clin Appl 6:304-8
Cai, Huan; Cong, Wei-na; Ji, Sunggoan et al. (2012) Metabolic dysfunction in Alzheimer's disease and related neurodegenerative disorders. Curr Alzheimer Res 9:5-17
Maudsley, Stuart (2012) G protein-coupled receptor biased agonism: development towards future selective therapeutics. Mini Rev Med Chem 12:803
Schwartz, Catherine M; Tavakoli, Tahereh; Jamias, Charmaine et al. (2012) Stromal factors SDF1*, sFRP1, and VEGFD induce dopaminergic neuron differentiation of human pluripotent stem cells. J Neurosci Res 90:1367-81
Abdelmohsen, Kotb; Srikantan, Subramanya; Tominaga, Kumiko et al. (2012) Growth inhibition by miR-519 via multiple p21-inducing pathways. Mol Cell Biol 32:2530-48
Martin, Bronwen; Chadwick, Wayne; Yi, Tie et al. (2012) VENNTURE--a novel Venn diagram investigational tool for multiple pharmacological dataset analysis. PLoS One 7:e36911
Stranahan, Alexis M; Martin, Bronwen; Chadwick, Wayne et al. (2012) Metabolic context regulates distinct hypothalamic transcriptional responses to antiaging interventions. Int J Endocrinol 2012:732975
Park, Sung-Soo; Wu, Wells W; Zhou, Yu et al. (2012) Effective correction of experimental errors in quantitative proteomics using stable isotope labeling by amino acids in cell culture (SILAC). J Proteomics 75:3720-32
Maudsley, Stuart; Chadwick, Wayne (2012) Progressive and unconventional pharmacotherapeutic approaches to Alzheimer's disease therapy. Curr Alzheimer Res 9:1-4

Showing the most recent 10 out of 52 publications