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Unfolded Proteins May Protect Cells from Dying

reticulum proteins together,' says Steller. 'Though we are not saying there couldn't be any cross-communication between these two pathways, I think our results show that the situation is considerably more complex than had been previously appreciated. The cell really knows where the stress is coming from, and whether the unfolded protein response is initiated in the endoplasmic reticulum or in the cytoplasm.'

Using the tools that Ryoo developed, Steller hopes that more aspects of the unfolded protein response pathway can be illuminated. While they found that the unfolded protein response initially protects retinal cells from death in the fly model of ADRP, the cells eventually die, leading to blindness. How the cell death pathway becomes activated is still a mystery, and Steller makes the point that although blocking cell death is a worthwhile therapeutic strategy, blocking it globally is not. Scientists still need to understand the specific proteins involved to create the most effective therapy.

'When it comes to avoiding cancer or defense against virally infected cells, cell death is a good thing,' says Steller. 'But when cells are stressed, and as a result are dying too easily, blocking the pathways that lead to the activation of cell death would be an ideal way to fight disease. Using this new technique, we can now go step by step down the pathway, not only identifying proteins that are functionally relevant to cell death, but also finding which will make the most attractive targets for pharmacological development.'

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