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. 2014 Jun 4;137(7):1894–1906. doi: 10.1093/brain/awu114

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© The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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The unfolded protein response illustrating the activation of PERK and increase of binding immunoglobulin protein (BiP), EIF2A-P, ATF4 and CHOP. One arm of the unfolded protein response, which appears to be elevated in motor neuron disease, is initiated by the activation of PERK. The schematic depicts this pathway and highlights the markers that are examined in this study (red boxes). They included: (1) BiP, a misfolded protein sensor; (2) ATF4, a transcription factor that is exempt from the global translational arrest that results is a consequence of the unfolded protein response; and (3) CHOP, a pro-apoptotic marker that is transcribed downstream of ATF4. ER = endoplasmic reticulum.