Convergent Activation of the Integrated Stress Response and ER–Mitochondria Uncoupling in VAPB-Associated ALS

Human iPSC-derived motor neurons with either VAPB WT or VAPB P56S expressed under the control of a doxycycline inducible promoter were grown out to day 35 of motor neuron differentiation. A co-immunoprecipitation was then performed using the VAPB protein as bait to determine the interactome of VAPB and the effect of the P56S mutation upon it, specifically within motor neurons, the affected cell type in ALS.