PA-00-019 Mentored Research Scientist Development Award (K01) """"""""Mechanisms of the Abeta sequestration in AD"""""""" The candidate, Yasuji Matsuoka, PhD, is a junior researcher with considerable experience in neuroscience research in Alzheimer's disease (AD). In order to become a fully independent translational neuroscientist in AD and other neurodegenerative diseases, an additional supervised training period is critical. The candidate is eager to expand his knowledge and techniques in both clinical and basic aspects of therapeutic research. Dr. Paul Aisen (Professor of Neurology and Medicine, and Director of the Memory Disorders Program at Georgetown University), will be the primary mentor for training in drug development for AD. Drs. Karen Gale (Professor of Pharmacology, Georgetown University) and Karen Duff (Associate Professor, Nathan Kline Institute / New York University) will be co-mentors to provide training in behavioral analysis using transgenic models of Alzheimer's disease. Additional consultants will provide expertise in basic research into neurodegeneration (Dr. Mattson), medicinal chemistry (Dr. Kozikowski) and neuroimaging (Dr. Fricke) Georgetown University Medical Center offers a stimulating scientific and clinical environment. The five year career development plan aims to: 1) provide the candidate a strong understanding and background in clinical drug development; 2) improve and extend his research experience and knowledge in behavioral analysis of AD mouse models; 3) assure ethical conduct in both clinical and basic research using human subjects and animals. The primary research goal of this proposal is the elucidation of a promising, novel therapeutic approach to AD, """"""""Abeta sequestration"""""""". The candidate has demonstrated that brain Aa can be altered using non-immune amyloid-binding compounds. The research studies proposed will investigate the pools and conformations of Aa that can be influenced by peripheral binding compounds, the ideal structure of such compounds, and blood-brain barrier transport of Abeta.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
1K01AG022455-01A1
Application #
6774530
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Snyder, Stephen D
Project Start
2004-09-01
Project End
2009-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
1
Fiscal Year
2004
Total Cost
$126,090
Indirect Cost
Name
Georgetown University
Department
Neurology
Type
Schools of Medicine
DUNS #
049515844
City
Washington
State
DC
Country
United States
Zip Code
20057
Niikura, Takako; Sidahmed, Elkhansa; Hirata-Fukae, Chiho et al. (2011) A humanin derivative reduces amyloid beta accumulation and ameliorates memory deficit in triple transgenic mice. PLoS One 6:e16259
Wu, Fangbai; Matsuoka, Yasuji; Mattson, Mark P et al. (2009) The clathrin assembly protein AP180 regulates the generation of amyloid-beta peptide. Biochem Biophys Res Commun 385:247-50
Takata, Kazuyuki; Kitamura, Yoshihisa; Nakata, Yukinori et al. (2009) Involvement of WAVE accumulation in Abeta/APP pathology-dependent tangle modification in Alzheimer's disease. Am J Pathol 175:17-24
Hirata-Fukae, Chiho; Li, Hui-Fang; Ma, Li et al. (2009) Levels of soluble and insoluble tau reflect overall status of tau phosphorylation in vivo. Neurosci Lett 450:51-5
Matsuoka, Yasuji; Andrews, Howard F; Becker, Amanda G et al. (2009) The relationship of plasma Abeta levels to dementia in aging individuals with Down syndrome. Alzheimer Dis Assoc Disord 23:315-8
Bernardo, Alexandra; Harrison, Fiona E; McCord, Meghan et al. (2009) Elimination of GD3 synthase improves memory and reduces amyloid-beta plaque load in transgenic mice. Neurobiol Aging 30:1777-91
Morales-Corraliza, Jose; Mazzella, Matthew J; Berger, Jason D et al. (2009) In vivo turnover of tau and APP metabolites in the brains of wild-type and Tg2576 mice: greater stability of sAPP in the beta-amyloid depositing mice. PLoS One 4:e7134
Hoe, Hyang-Sook; Minami, S Sakura; Makarova, Alexandra et al. (2008) Fyn modulation of Dab1 effects on amyloid precursor protein and ApoE receptor 2 processing. J Biol Chem 283:6288-99
Hirata-Fukae, Chiho; Li, Hui-Fang; Hoe, Hyang-Sook et al. (2008) Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model. Brain Res 1216:92-103
Matsuoka, Yasuji; Jouroukhin, Yan; Gray, Audrey J et al. (2008) A neuronal microtubule-interacting agent, NAPVSIPQ, reduces tau pathology and enhances cognitive function in a mouse model of Alzheimer's disease. J Pharmacol Exp Ther 325:146-53

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