Endoplasmic reticulum stress response as a potential therapeutic target in multiple sclerosis

This schematic diagram of the ERSR pathway includes how expression levels of several of the genes encoding ERSR proteins are altered during EAE. EAE was induced by priming SJL mice with proteolipid protein (PLP) 139–151 peptide emulsified in Freund’s complete adjuvant. At the peak of disease, lesion and peri-lesion regions of spinal cords from EAE mice, as well as comparable regions from the spinal cords of naïve SJL mice, were collected by laser dissection, and a gene array was performed. The color and direction of the arrows indicate which genes were up- or down-regulated for each region in comparison to the others. Lesions consist of multiple cell types and therefore these data may not give an accurate picture at a cellular level, and it is quite clear that the changes in gene expression within the pathway are heterogeneous. However, a trend for upregulation of genes that are important in activating pro-apoptotic signals such as ATF4 and ATF6 was evident within EAE lesion compared to peri-lesion and naive controls. Many of the genes in the PERK part of the ERSR pathway were downregulated in lesions. Further work at a protein level is required to confirm these data.

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Endoplasmic reticulum stress response as a potential therapeutic target in multiple sclerosis. () Meghann Teague Getts, et al. Therapy. ;5(5):631-640. Figure: F1. All organisms Mus musculus Homo sapiens Rattus norvegicus Drosophila melanogaster

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