Longitudinal study of differential protein expression in an Alzheimer's mouse model lacking inducible nitric oxide synthase.
Longitudinal study of differential protein expression in an Alzheimer's mouse model lacking inducible nitric oxide synthase.
复制标题
DOI：
10.1021/pr4005103
复制
发表时间：
2013-10-04
影响因子：
4.4
通讯作者：
Colton CA
中科院分区：
文献类型：
--
作者：
Hoos MD;Richardson BM;Foster MW;Everhart A;Thompson JW;Moseley MA;Colton CA
Alzheimer’s disease (AD) is a complex neurodegenerative process that involves altered brain immune, neuronal and metabolic functions. Understanding the underlying mechanisms has relied on mouse models that mimic components of AD pathology. We used gel-free, label-free LC/MS/MS to quantify protein and phosphopeptide levels in brains of APPSwDI/NOS2−/− (CVN-AD) mice. CVN-AD mice show a full spectrum of AD-like pathology, including amyloid deposition, hyperphosphorylated and aggregated tau and neuronal loss that worsens with age. Tryptic digests, with or without phosphopeptide enrichment on an automated titanium dioxide LC system, were separated by on-line two-dimensional LC and analyzed on a Waters Synapt G2 HDMS, yielding relative expression for >950 proteins and >1100 phosphopeptides. Among differentially expressed proteins were known markers found in humans with AD, including GFAP and C1Q. Phosphorylation of connexin 43, not previously described in AD, was increased at 42 weeks, consistent with dysregulation of gap junctions and activation of astrocytes. Additional alterations in phosphoproteins suggests dysregulation of mitochondria, synaptic transmission, vesicle trafficking and innate immune pathways. These data validate the CVN-AD mouse model of AD, identify novel disease and age-related changes in the brain during disease progression and demonstrate the utility of integrating unbiased and phosphoproteomics for understanding disease processes in AD.
登录
查看更多内容
影响因子：
3.3
作者：
Di Domenico, Fabio;Sultana, Rukhsana;Barone, Eugenio;Perluigi, Marzia;Cini, Chiara;Mancuso, Cesare;Cai, Jian;Pierce, William M.;Butterfield, D. Allan
通讯作者：
Butterfield, D. Allan
影响因子：
4.8
作者：
Davis, J;Xu, F;Van Nostrand, WE
通讯作者：
Van Nostrand, WE
shot弹枪蛋白质组学的二维分级技术的比较。
影响因子：
7.4
作者：
Dowell, James A.;Frost, Dustin C.;Zhang, Jiang;Li, Lingjun
通讯作者：
Li, Lingjun
DOI：
10.1523/jneurosci.3932-10.2011
发表时间：
2011-03-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Benoit ME;Tenner AJ
通讯作者：
Tenner AJ
DOI：
10.1073/pnas.0601075103
发表时间：
2006-08-22
影响因子：
11.1
作者：
Colton, C. A.;Vitek, M. P.;Dawson, H.
通讯作者：
Dawson, H.