In addition to the PERK-ATF4-CHOP axis, other key ER stress pathways, such as IRE1/XBP1 and ATF6 also contribute to the UPR, collectively managing protein misfolding and restoring homeostasis, or, if stress persists, trigger cell death (Tabas and Ron, 2011)
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These concerns are being addressed in a current phase 3, double-blind, randomized, placebo-controlled, multicenter study of Voxelotor (ClinicalTrials.gov Identifier: NCT03036813) (Vichinsky et al., 2019)
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Kasztelan-Szczerbinska B, Cichoz-Lach H