However, according to our result, the exact GO modules of alpha estradiol was mainly associated with lipid process, while monorden showed strong connec tion with sterol selleck Abiraterone process. The two different processes indi cated that Hsp90 should have a second pathway to con nect with AD. Compared with GO categories of alpha estradiol and monoden, fulvestrant had two additional categories, phosphoglyceride metabolic process and phospholipid biosynthetic process, listed. Based on these, we hypothesize that estrogen might act the Inhibitors,Modulators,Libraries phospholipid pathway designed to alleviate AD. Literature mining helped us reveal that estrogen reduced the risk of AD by anti Ab. Estrogen accelerated bAPP trafficking and pre cludesmaximal Ab generation within the TGN by mod ulating TGN phospholipid levels, particularly those of phosphatidylinositol.
Therefore, fulvestrant, as estrogen blocker might activate phospholipid Inhibitors,Modulators,Libraries pathway to acceler ate b amyloid and aggravate AD. Based on our analy Despite that both estrogen receptor and Hsp90 inhibitors are promis ing drug targets for AD, estrogen receptor is a much better Inhibitors,Modulators,Libraries candidate. The success of three cases between mouse models and human demonstrated that our cross species analysis method was able to assess animal models similarity to humans disease state. Inhibitors,Modulators,Libraries The main basis may be that orthologous genes were not only conserved at the sequence level and perform similar functions in different organisms, but also the corresponding gene expression patterns were conserved on a global level, especially between the human and mouse.
Our result that microarrays of cell response to molecules or drugs showed similarity across cell lines or tissues, to some extent, also explained why our approach was feasible to test mouse models. Nevertheless, as the diabetes drug case showed, it should be noticed that intrinsic Inhibitors,Modulators,Libraries differ ences always existed in normal and pathobiology states between species. Therefore, it was sometimes not appropriate for an animal model to mimic human dis eases or drug response. Our method based on the analy sis of the relationship of function known drugs and human diseases utilizing microarray expression data per formed well in both situations. Additionally, due to the introduction of GO annotations and the application of the statistical analysis, this cross species method was able to provide bidirectional relationship between drugs and disease, and more clues about potential biological mechanisms.
By contrast, the distance method seemed to be oversimplified and couldnt provide such information. In this paper, we presented data only from mouse ani mal models, for the mouse was the main model for common human diseases. At present, the National Cen ter for Biotechnology Information Gene Expres sion Omnibus enrolled 1295 datasets on homo selleck kinase inhibitor sapiens and 1069 datasets on Mus musculus.