%0 Journal Article
%T Dynamic alteration of neprilysin and endothelin-converting enzyme in age-dependent APPswe/PS1dE9 mouse model of Alzheimer¡¯s disease
%A Chunsheng Wei
%A Dong Dong
%A Jianxu Liu
%A Li Zhou
%A Rui Wang
%J Archive of "American Journal of Translational Research".
%D 2017
%X Imbalance of A¦Â production and A¦Â removal leads to A¦Â accumulation. A¦Â degrading enzyme (including neprilysin-NEP, endothelin converting enzyme-ECE) as a therapeutic strategy for lowering brain A¦Â deposition has attracted increasing attention. In this study, we investigated alteration of age and region-dependent in APP/PS1 double transgenic mice (3, 6, 9, 12 months) and their age-matched wild type mice including the ability of spatial memory, A¦Â deposits, the protein expression, location and activity of NEP and ECE. Our data demonstrated that, as compared with wild type mice, APP/PS1 mice displayed significant cognitive deficit at 9 month revealed by obviously longer in the latency and distance to find the platform and shorter in time spent and swimming distance in the target quadrant. A¦Â40 and A¦Â42 levels exhibited a significant increase with age in the cerebral cortex and hippocampus of APP/PS1 mice after 6 month, compared with their age-matched wild type mice. And A¦Â42 levels were significantly higher than A¦Â40 levels in the same age of APP/PS1 mice. Furthermore, NEP protein and activity displayed a marked decrease with age in the cerebral cortex and hippocampus of APP/PS1 mice older than 6 month. Slightly different from NEP, ECE protein was up-regulated with age, while ECE activity showed a significantly decrease with age in cortex and hippocampus of APP/PS1 mice older than 6 month. Double immunofluorescence staining also demonstrated that ECE and NEP highly colocalized in cytoplasmic and membrane, and ECE immunoreactivity tended to increase with age in APP/PS1 mice, especially 12 month APP/PS1 mice. Correlation analysis showed the negative correlation between enzyme (NEP or ECE) activity and A¦Â levels in the cerebral cortex and hippocampus of APP/PS1 mice, which was correlated with A¦Â accumulation. These results indicate NEP rather than ECE plays more important role in resisting A¦Â accumulation. The compensatory upregulation of NEP and ECE could balance A¦Â metabolism and protect neuronal functions in infant and juvenile mice. These evidence might provide some clues for the treatment of Alzheimer¡¯s disease
%K A¦Â
%K neprilysin
%K endothelin converting enzyme
%K colocalization
%K enzyme activity
%K Alzheimer¡¯s disease
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5250715/