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

Chandler L. WALKER, Nai-Kui LIU, Xiao-Ming XU

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Front. Biol. ›› 2013, Vol. 8 ›› Issue (4) : 421-433. DOI: 10.1007/s11515-013-1255-1
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PTEN/PI3K and MAPK signaling in protection and pathology following CNS injuries

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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 mitogen-activated 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.

Keywords

spinal cord injury / traumatic brain injury / PTEN / MAPK / neuroprotection / axon regeneration

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Chandler L. WALKER, Nai-Kui LIU, Xiao-Ming XU. PTEN/PI3K and MAPK signaling in protection and pathology following CNS injuries. Front Biol, 2013, 8(4): 421‒433 https://doi.org/10.1007/s11515-013-1255-1

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Acknowledgments

This work was supported by National Institutes of Health (NIH/NINDS R01 NS059622, NS050243, NS073636 to XMX, and F31 NS 071863 to CLW), the Indiana Spinal Cord and Brain Injury Research Funds, the Mari Hulman George Endowment Funds. We also appreciate the use of the Core facility of the Spinal Cord and Brain Injury Research Group/Stark Neurosciences Research Institute at Indiana University.

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2014 Higher Education Press and Springer-Verlag Berlin Heidelberg
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