• Journal of neurotrauma · Feb 2018

    ATF6α deletion modulates the ER stress response after spinal cord injury but does not affect locomotor recovery.

    • Saraswat Ohri Sujata S 1 Kentucky Spinal Cord Injury Research Center, University of Louisville , Louisville, Kentucky. , Ashley Mullins, Michal Hetman, and Scott R Whittemore.
    • 1 Kentucky Spinal Cord Injury Research Center, University of Louisville , Louisville, Kentucky.
    • J. Neurotrauma. 2018 Feb 1; 35 (3): 486-491.

    AbstractThe endoplasmic reticulum stress response (ERSR) is activated in a variety of neurodegenerative diseases and/or traumatic injuries. Subsequent restoration of ER homeostasis may contribute to improvement in the functional outcome of these diseases. We recently demonstrated improvements in hindlimb locomotion after thoracic spinal cord injury (SCI) and implicated oligodendrocyte survival as a potential mechanism using genetic and pharmacological inhibition of the protein kinase ribonucleic acid-like ER kinase- CCAAT/enhancer binding homologous protein (PERK-CHOP) arm of the ERSR. Here, we investigated the contribution of activating transcription factor-6 (ATF6), an ERSR signaling effector comprising the second arm of ERSR, in the pathogenesis of SCI. In contrast to what was seen after attenuation of PERK-CHOP signaling, genetic ablation of ATF6 results in modulation of ERSR and decreased survival in oligodendrocyte precursor cells against ER stress. Further, ATF6 loss delays the ERSR after SCI, potentiates PERK-ATF4-CHOP signaling and fails to improve locomotor deficits. These data suggest that deleting ATF6 levels is unlikely to be a viable therapeutic target to improve functional recovery after SCI.

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