Proteome analysis in mice expressing P301L tau

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DESCRIPTION (provided by applicant): 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