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  • Title: AMP-activated protein kinase-dependent induction of autophagy by erythropoietin protects against spinal cord injury in rats.
    Author: Wang P, Xie ZD, Xie CN, Lin CW, Wang JL, Xuan LN, Zhang CW, Wang Y, Huang ZH, Teng HL.
    Journal: CNS Neurosci Ther; 2018 Dec; 24(12):1185-1195. PubMed ID: 29656591.
    Abstract:
    AIMS: Autophagy has been regarded as a promising therapeutic target for spinal cord injury (SCI). Erythropoietin (EPO) has been demonstrated to exhibit neuroprotective effects in the central nervous system (CNS); however, the molecular mechanisms of its protection against SCI remain unknown. This study aims to investigate whether the neuroprotective effects of EPO on SCI are mediated by autophagy via AMP-activated protein kinase (AMPK) signaling pathways. METHODS: Functional assessment and Nissl staining were used to investigate the effects of EPO on SCI. Expressions of proteins were detected by Western blot and immunohistochemistry. RESULTS: Treatment with EPO significantly reduced the loss of motor neurons and improved the functional recovery following SCI. Erythropoietin significantly enhanced the SCI-induced autophagy through activating AMPK and inactivating mTOR signaling. The inhibitor of AMPK, compound C, could block the EPO-induced autophagy and beneficial action on SCI, whereas the activator of AMPK, metformin, could mimic the effects of EPO. In the in vitro studies, EPO enhanced the hypoxia-induced autophagy in an AMPK-dependent manner. CONCLUSIONS: The AMPK-dependent induction of autophagy contributes to the neuroprotection of EPO on SCI.
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