Ras family small GTPase-mediated neuroprotective signaling in stroke.
Ras family small GTPase-mediated neuroprotective signaling in stroke.
复制标题
RAS家族小GTPase介导的中风中的神经保护信号传导。
DOI：
10.2174/187152411796011349
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发表时间：
2011-06-01
影响因子：
--
通讯作者：
Cai W
中科院分区：
文献类型：
--
作者：
Shi GX;Andres DA;Cai W
选择性神经元细胞死亡是中风后神经元损伤的主要原因之一，脑细胞自然地调动多种生存信号通路来防止缺血。重要的是，旨在改善内源性抗凋亡信号传导的治疗策略似乎在中风治疗中具有广阔的前景。虽然中风的发病机制涉及多种复杂的机制，但控制细胞生存和死亡之间平衡的总体机制尚不明确。 Ras 家族小 GTP 酶在缺血性损伤后被激活，进而充当调节神经元存活和再生的内在开关。它们整合不同细胞内信号转导途径的能力使它们成为中风后神经元恢复的关键调节剂和潜在治疗靶点。本文重点介绍了 Ras 家族 GTPases 对神经保护信号级联的贡献，包括丝裂原激活蛋白激酶 (MAPK) 家族蛋白激酶和 AKT/PKB 依赖性信号通路，以及中风中 cAMP 反应元件结合 (CREB)、叉头盒 O (FoxO) 和缺氧诱导因子 1 (HIF1) 转录因子的调节。
Selective neuronal cell death is one of the major causes of neuronal damage following stroke, and cerebral cells naturally mobilize diverse survival signaling pathways to protect against ischemia. Importantly, therapeutic strategies designed to improve endogenous anti-apoptotic signaling appear to hold great promise in stroke treatment. While a variety of complex mechanisms have been implicated in the pathogenesis of stroke, the overall mechanisms governing the balance between cell survival and death are not well-defined. Ras family small GTPases are activated following ischemic insults, and in turn, serve as intrinsic switches to regulate neuronal survival and regeneration. Their ability to integrate diverse intracellular signal transduction pathways makes them critical regulators and potential therapeutic targets for neuronal recovery after stroke. This article highlights the contribution of Ras family GTPases to neuroprotective signaling cascades, including mitogen-activated protein kinase (MAPK) family protein kinase- and AKT/PKB-dependent signaling pathways as well as the regulation of cAMP response element binding (CREB), Forkhead box O (FoxO) and hypoxia-inducible factor 1(HIF1) transcription factors, in stroke.