ER-assisted folding
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.
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.
References
Wiseman RL, Balch WE. A new pharmacology—drugging stressed folding pathways. Trends Mol Med. 2005 Aug;11(8):347-50. PMID: #16005683#