Walker Chandler L, Liu Nai-Kui, Xu Xiao-Ming
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, 46202, USA ; Department of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, 46202, USA ; Departmentof Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana, 46202, USA ; Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, Indiana, 46202, USA.
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, 46202, USA ; Departmentof Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana, 46202, USA ; Goodman Campbell Brain and Spine, Indiana University School of Medicine, Indianapolis, Indiana, 46202, USA.
Front Biol (Beijing). 2013 Aug 1;8(4). doi: 10.1007/s11515-013-1255-1.
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.
脑和脊髓损伤通过坏死和程序性细胞死亡机制引发广泛的时空性神经退行性变。创伤性损伤会引发炎症、活性氧化、兴奋性毒性以及代谢过程的细胞特异性失调，这些都是造成这种累积性损伤的主要因素。成功的治疗依赖于预防或减轻破坏的程度，而通过调节信号级联反应来干扰有害的细胞反应是一种有效的方法。两条细胞内信号通路，即磷酸酶和张力蛋白同源物（PTEN）/磷脂酰肌醇3激酶（PI3K）和丝裂原活化蛋白激酶（MAPK）信号级联反应，在正常和病理条件下发挥着多种细胞作用。这两条通路的激活都能影响多种中枢神经系统疾病的解剖学和功能结局。然而，在传播特定的下游效应方面，一些机制涉及抑制或增强其中一条通路，或两条通路都抑制或增强。尽管许多细胞内机制促成了细胞对损伤的反应，但本综述探讨了有关PTEN/PI3K和MAPK信号对病理、神经保护和修复的影响的证据，以及如何针对这些通路来增进认识并改善脑和脊髓损伤后的神经学结局。
