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During ER stress, the expression of ER stress response genes (GRP78/BiP, CHOP, and ATF4) have been shown to be up-regulated. ER stress can be induced by many factors, including pathophysiological conditions (hyper-homocysteinemia, neurotrophic factor deprivation, and hypoxia) and pharmacological agents which can trigger the unfolded protein response and induce cellular dysfunction.