Friday, 7 February 2014

What proteins are there in MS lesions?

Raddatz BB, Hansmann F, Spitzbarth I, Kalkuhl A, Deschl U, Baumgärtner W, Ulrich R.Transcriptomic meta-analysis of multiple sclerosis and its experimental models. PLoS One. 2014 Jan 27;9(1):e86643.


BACKGROUND:Multiple microarray analyses of multiple sclerosis (MS) and its experimental models have been published in the last years.
OBJECTIVE:Meta-analyses integrate the information from multiple studies and are suggested to be a powerful approach in detecting highly relevant and commonly affected pathways.
DATA SOURCES: ArrayExpress, Gene Expression Omnibus and PubMed databases were screened for microarray gene expression profiling studies of MS and its experimental animal models.
MATERIAL AND METHODS: Included conditions for re-analysis of differentially expressed genes (DEGs) were MS, myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) in rats, proteolipid protein-induced EAE in mice, Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), and a transgenic tumor necrosis factor-overexpressing mouse model (TNFtg). Since solely a single MS raw data set fulfilled the inclusion criteria, a merged list containing the DEGs from two MS-studies was additionally included. Cross-study analysis was performed employing list comparisons of DEGs and alternatively Gene Set Enrichment Analysis (GSEA).
RESULTS: The intersection of DEGs in MS, EAE, TMEV-IDD, and TNFtg contained 12 genes related to macrophage functions. The intersection of EAE, TMEV-IDD and TNFtg comprised 40 DEGs, functionally related to positive regulation of immune response. Over and above, GSEA identified substantially more differentially regulated pathways including coagulation and JAK/STAT-signaling.
CONCLUSION: A meta-analysis based on a simple comparison of DEGs is over-conservative. In contrast, the more experimental GSEA approach identified both, a priori anticipated as well as promising new candidate pathways.
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Looking at upregulated genes in pathways found 12 found in MS and all MS models

The aims of the present study were 1.) to re-analyze publicaly available microarray data sets of MS and its animal models employing a consistent methodology, 2.) to compare the results across species, experimental models and platforms in order to detect highly conserved pathways that offer the broadest therapeutic potential, and 3.) to explore, if the transcriptional changes in the different animal models reflect the anticipated difference in the pathomechanisms.

T
his study looked at protein production using array chips that allow you to scan all known genes in the genome.


In studies it was found that there were genes that are either up or down regulated in MS plaques were looked at and there were out 4000. Myelination genes were down regulated in tissues that would contain demyelination  but there was little consenus and the overlap was about 12 genes shared with MS and animal models. 

However, if you compare apples and oranges you may not expect similarity as the early lesions in EAE full ofT cells and limited demyelination is not that similar to a demyelinated plaque within an active macrophage filled lesions. Many of the expressed genes are found in certain cell types and so they crop up in microarray just because the cell is there. 

However some will use this to say how different animals are from humans, but as it is open access you can read it and make your own mind

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