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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

A new pharmacology--drugging stressed folding pathways.

Folding in the endoplasmic reticulum (ER) must couple protein-synthesis pathways operating outside of the compartment with ER-assisted folding (ERAF) pathways in the lumen. Chaperone-mediated folding imbalances that are associated with numerous misfolding diseases, including diabetes, trigger the unfolded-protein response (UPR), using both transcriptional and translational pathways to correct the problem. Recent work suggests that small-molecule inhibitors could be useful to help rebalance protein synthesis with ERAF pathways through the ribosomal initiating factor eIF2alpha. Reprogramming stress pathways with drugs provides a potential new approach for balancing ER-protein load with cellular-folding capacity, thus correcting disease.[1]


  1. A new pharmacology--drugging stressed folding pathways. Wiseman, R.L., Balch, W.E. Trends in molecular medicine. (2005) [Pubmed]
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