The use of proteome analysis in disease investigations has been instrumental for the study of tissue, subcellular compartments, and even protein complexes in the quest to identify biomarkers for the diagnosis and early detection of several diseases. We intend to employ this high throughput technology in the analysis of tau and other proteins during the development of tauopathy in the FTDP-17 mouse model JNPL3, which expresses the human 4RON tau isoform bearing the P301L missense mutation. Previous studies demonstrated that in FTDP-17 P301L tau proteins undergo age- and pathological-dependent hyperphosphorylation, suggesting that aberrant tau phosphorylation may play an important role in the onset and/or progression of tauopathy. Furthermore, preliminary results in our laboratory showed that several proteins are differentially expressed between JNPL3 and non-transgenic littermates. In order to further characterize these changes mass spectroscopy-based phosphopeptide analysis will be employed in the quest to identify tau phosphorylation events at different stages in the development of tauopathy in the JPNL3 mice. In addition, a proteome analysis of fractionated proteins from brain and spinal cord tissues will be used for the identification, and subsequent characterization of proteins involved in and/or affected by tau aggregation. These approaches may contribute to the identification of important biological markers involved at early stages of the development of tauopathy and may bring insights into the molecular mechanism underline tau aggregation ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS047930-02
Application #
6844690
Study Section
Special Emphasis Panel (ZRG1-F03A (20))
Program Officer
Murphy, Diane
Project Start
2004-01-01
Project End
2005-11-30
Budget Start
2005-01-01
Budget End
2005-11-30
Support Year
2
Fiscal Year
2005
Total Cost
$45,309
Indirect Cost
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Vega, Irving E; Hamano, Tadanori; Propost, Josh A et al. (2006) Taxol and tau overexpression induced calpain-dependent degradation of the microtubule-destabilizing protein SCG10. Exp Neurol 202:152-60
Vega, Irving E; Cui, Li; Propst, Josh A et al. (2005) Increase in tau tyrosine phosphorylation correlates with the formation of tau aggregates. Brain Res Mol Brain Res 138:135-44