It is becoming clear that multiple forms of cognitive ability or susceptibility to neurodegenerative disorders are affected by general systemic metabolic function. Thus, cognitive health is tightly linked to metabolic health. Previously, we have already pioneered this work by linking the progression of Huntingtons disease to a diabetic-like state. It is clear from several lines of evidence, including our own, that hormones responsible for metabolic regulation also play vital roles in cognitive function. For example, we have previously shown that Exendin-4, which is a long-acting analogue of the gut hormone Glucagon-like peptide 1 (GLP-1) can improve euglycemia, protect pancreatic islet function, improve motor coordination and reduce mutant huntingin aggregates in a mouse model of Huntingtons disease. It is likely that through the creation of multiple types of metabolically-targeted therapeutics, there will also be the creation of distinct mechanisms by which these strategies affect cognitive function. Currently we are investigating underlying metabolic dysunction in various neurological disorders, such as Alzheimer's disease, Huntington's disease, Autism Spectrum disorder, Post-partum depression, and WAGR syndrom. Our goal is to first understand how multiple types of glycemic and metabolic control can affect neuronal function and then to tailor distinct novel therapeutics which can maintain or enhance both metabolic and cognitive function.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAAG000917-03
Application #
8552505
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2012
Total Cost
$366,175
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
Zip Code
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
Martin, Bronwen; Chadwick, Wayne; Cong, Wei-na et al. (2012) Euglycemic agent-mediated hypothalamic transcriptomic manipulation in the N171-82Q model of Huntington disease is related to their physiological efficacy. J Biol Chem 287:31766-82
Rothman, Sarah M; Herdener, Nathan; Camandola, Simonetta et al. (2012) 3xTgAD mice exhibit altered behavior and elevated Aβ after chronic mild social stress. Neurobiol Aging 33:830.e1-12
Maudsley, S; Patel, S A; Park, S-S et al. (2012) Functional signaling biases in G protein-coupled receptors: Game Theory and receptor dynamics. Mini Rev Med Chem 12:831-40
Siddiqui, Sana; Fang, Meng; Ni, Bin et al. (2012) Central role of the EGF receptor in neurometabolic aging. Int J Endocrinol 2012:739428
Chadwick, Wayne; Mitchell, Nicholas; Martin, Bronwen et al. (2012) Therapeutic targeting of the endoplasmic reticulum in Alzheimer's disease. Curr Alzheimer Res 9:110-9
Driscoll, Ira; Martin, Bronwen; An, Yang et al. (2012) Plasma BDNF is associated with age-related white matter atrophy but not with cognitive function in older, non-demented adults. PLoS One 7:e35217
Wu, Wells W; Wang, Guanghui; Insel, Paul A et al. (2012) Discovery- and target-based protein quantification using iTRAQ and pulsed Q collision induced dissociation (PQD). J Proteomics 75:2480-7
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
Chadwick, Wayne; Martin, Bronwen; Chapter, Megan C et al. (2012) GIT2 acts as a potential keystone protein in functional hypothalamic networks associated with age-related phenotypic changes in rats. PLoS One 7:e36975

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