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New Protein Targets Found in Multiple Sclerosis

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There may be no bigger disease to study at the intersection of immunology and neurology than multiple sclerosis. Which is why Lawrence Steinman, a neurologist and head of Stanford University's immunology department, has focused his research efforts on understanding the pathogenesis of this debilitating disease since 1975. Recently, Steinman and his colleagues discovered several potential therapeutic targets for the autoimmune disease using a proteomics approach. The investigators were able to identify proteins unique to MS lesions including acute plaque, chronic plaque, and chronic active plaque found in the central nervous system white matter.

Researchers have for some time relied upon transcriptome analysis to investigate MS, says Steinman, but this approach does not allow much insight into the functional aspects of the actual cause of the disease. "Not every transcript leads to a transcribed protein because proteins get modified post-translationally — so some transcripts are more abundant, but the protein is of less importance. In other instances, transcripts are in very low abundance and you might miss it," Steinman says. "Primarily, one is interested in the products that are mediating the biological effect and it's not the transcripts, it's the proteins, lipids, and sugars."

In 2002, his group published a transcript analysis of gene microarrays of the exact same MS tissue, but the team thought it would be a good idea to try a proteomics approach this time around. "What proteomics generates is a list, and to our astonishment, about half the proteins according to the informatics that we did were of unknown function. And then some of the proteins were of known function, or at least we think we know what the function is," Steinman says. "So I chose to take an approach where we would try to look at the proteins where we think we know the function but they might be playing a different role."

While there have been some proteomic approaches applied to MS prior to Steinman's recent work, many of these efforts were primarily focused on lymphocytes and spinal fluid. This study marks the first time that proteomics has been used to analyze specifically defined lesions in brain tissue. Steinman, who says that these findings represent the tip of a "very interesting iceberg," is set to publish a comparison of the transcriptomic and proteomic techniques that he says will demonstrate a high rate of concordance between the transcripts and proteins.

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