This oxidative damage was GSK J4 mw dependent on the methionine 35 residue within the A beta peptide. Further insight into the molecular pathways affected in this Tg model

of AD may be gained with discovery-based proteomics studies; therefore, two-dimensional gel-based expression proteomics was performed to compare differences in brain protein levels of J20 Tg mice with non-transgenic (NTg) littermate controls. Based on our studies, we identified six proteins that had significantly increased levels in J20 Tg relative to NTg mice: calcineurin subunit B type 1, rho GDP-dissociation inhibitor 1, T-complex protein 1 subunit alpha A, alpha-enolase, peptidyl-prolyl cis-trans isomerase (Pin-1), and ATP synthase subunit alpha mitochondrial. Several of these proteins have previously

been implicated in in vitro and in vivo models and subjects with AD. Additionally, using redox proteomics analyses we identified two oxidatively-modified proteins: phosphatidylethanolamine-binding protein 1 and Pin-1 with decreased levels of protein 3-nitrotyrosine in J20 Tg mice relative to NTg. Western blotting and immunoprecipitation analyses were used to validate proteomics results. PD0332991 Overall, these studies provide information about changes in the brain proteome as a result of A beta deposition and clues with which to further direct studies on elucidating AD pathogenesis. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Methionine sulfoxide reductase A knockout (MsrA(-/-)) mice, which serve as a potential model for neurodegeneration, suffer from increased oxidative stress and have previously been found to have

chronically elevated brain dopamine (DA) content levels relative to control mice. Additionally, these high levels parallel the increased presynaptic DA release. In this study, fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes was used to quantify striatal reserve pool DA in knockout mice and wild-type control mice. Reserve pool DA efflux, induced by amphetamine (AMPH), was measured in brain slices from knockout and wild type (WT) mice in the presence of alpha-methyl-p-tyrosine, a DA synthesis inhibitor. Additionally, the stimulated release of reserve pool DA, mobilized by cocaine (COC), was measured. Both efflux and Acetophenone stimulated release measurements were enhanced in slices from knockout mice, suggesting that these mice have greater reserve pool DA stores than wild-type and that these stores are effectively mobilized. Moreover, dopamine transporter (DAT) labeling data indicate that the difference in measured DA efflux was likely not caused by altered DAT protein expression. Additionally, slices from MsrA(-/-) and wild-type mice were equally responsive to increasing extracellular calcium concentrations, suggesting that potential differences in either calcium entry or intracellular calcium handling are not responsible for increased reserve pool DA release.