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PTEN/PI3K and MAPK signaling in protection and pathology following CNS injuries

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  • Published:
Frontiers in Biology

Abstract

Brain and spinal cord injuries initiate widespread temporal and spatial neurodegeneration, through both necrotic and programmed cell death mechanisms. Inflammation, reactive oxidation, excitotoxicity and cell-specific dysregulation of metabolic processes are instigated by traumatic insult and are main contributors to this cumulative damage. Successful treatments rely on prevention or reduction of the magnitude of disruption, and interfering with injurious cellular responses through modulation of signaling cascades is an effective approach. Two intracellular signaling pathways, the phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3-kinase (PI3K) and mitogenactivated protein kinase (MAPK) signaling cascades play various cellular roles under normal and pathological conditions. Activation of both pathways can influence anatomical and functional outcomes in multiple CNS disorders. However, some mechanisms involve inhibiting or enhancing one pathway or the other, or both, in propagating specific downstream effects. Though many intracellular mechanisms contribute to cell responses to insult, this review examines the evidence exploring PTEN/PI3K and MAPK signaling influence on pathology, neuroprotection, and repair and how these pathways may be targeted for advancing knowledge and improving neurological outcome after injury to the brain and spinal cord.

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Authors and Affiliations

  1. Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Chandler L. Walker, Nai-Kui Liu & Xiao-Ming Xu

  2. Department of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Chandler L. Walker & Xiao-Ming Xu

  3. Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Chandler L. Walker, Nai-Kui Liu & Xiao-Ming Xu

  4. Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Chandler L. Walker, Nai-Kui Liu & Xiao-Ming Xu

Authors
  1. Chandler L. Walker
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  2. Nai-Kui Liu
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  3. Xiao-Ming Xu
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Correspondence to Xiao-Ming Xu.

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Walker, C.L., Liu, NK. & Xu, XM. PTEN/PI3K and MAPK signaling in protection and pathology following CNS injuries. Front. Biol. 8, 421–433 (2013). https://doi.org/10.1007/s11515-013-1255-1

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  • DOI: https://doi.org/10.1007/s11515-013-1255-1

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