Boyce M, Bryant KF, Jousse C, Long K, Harding HP, Scheuner D, Kaufman RJ, Ma D, Coen DM, Ron D, Yuan J.
A selective inhibitor of eIF2alpha dephosphorylation protects cells from ER stress.
Science. 2005 Feb 11;307(5711):935-9.
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This is a very interesting paper. Boyce and colleagues showed that pharmacological inhibition of dephosphorylation of eukaryotic initiator factor 2α increases its activity, thus protecting against the effects of ER stress. They also demonstrated that this effect slows down HSV replication.
However, these important findings do not seem to have a direct application in Alzheimer disease. ER stress, and the consequent UPR, are not implicated in β amyloid production, or in APP processing, as shown by my and other's groups (Siman et al., 2001; Piccini et al., 2004). Instead, inhibition of the effects of ER stress may be potentially beneficial in neurodegenerative disorders characterized by intracellular toxic aggregates, such as Parkinson disease and tauopathies, in which ER stress may contribute to the creation of misfolded peptides.