Overcoming Stress

Abstract

Diverse human diseases such as viral infections, diabetes, and neurodegeneration are characterized at the cellular level by an inability of the endoplasmic reticulum (ER) to fold proteins properly, resulting in the onset of "ER stress." Uncorrected ER stress activates apoptotic cell death pathways, and it has been hypothesized that these pathways might be manipulated for therapeutic benefit. In a chemical screen, Boyce et al. identified a small molecule (salubrinal) that protects cells from ER-stress-induced apoptosis. Salubrinal selectively inhibited the dephosphorylation of eukaryotic translation initiation factor α (eIF2α) and inhibited herpesvirus replication. Thus, eIF2α may be a valuable drug target for diseases involving ER stress. M. Boyce, K. F. Bryant, C. Jousse, K. Long, H. P. Harding, D. Scheuner, R. J. Kaufman, D. Ma, D. M. Coen, D. Ron, J. Yuan, A selective inhibitor of eIF2α dephosphorylation protects cells from ER stress. Science 307, 935-939 (2005). [Abstract] [Full Text]