Blocking the phosphatidylinositol 3-kinase pathway inhibits neuregulin-1-mediated rescue of neurotoxicity induced by A1-42
Blocking the phosphatidylinositol 3-kinase pathway inhibits neuregulin-1-mediated rescue of neurotoxicity induced by A1-42
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DOI：
10.1111/jphp.12563
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发表时间：
2016-08-01
影响因子：
3.3
通讯作者：
Woo, Ran-Sook
中科院分区：
文献类型：
--
作者：
Baik, Tai-Kyoung;Kim, Young-Jung;Woo, Ran-Sook
目的神经调节蛋白1（Neuregulin-1，NRG 1）在脑的发育和可塑性中起重要作用，并具有神经保护作用。在这项研究中，我们研究了NRG 1信号传导的下游途径及其在预防A（1-42）诱导的神经毒性中的作用。通过测定超氧化物歧化酶（SOD）活性和TUNEL染色，检测原代大鼠皮层神经元的神经保护特性。Akt激活取消了NRG 1的能力，以防止A（1-42）诱导的LDH释放和增加TUNEL阳性细胞计数和活性氧在原代cortex neurons.ConclusionsOur结果表明，NRG 1信号传导对A（1-42）诱导的神经毒性通过激活PI 3 K/Akt通路发挥神经保护作用。此外，这表明NRG 1具有治疗AD的神经保护潜力。
ObjectivesNeuregulin-1 (NRG1) has an important role in both the development and the plasticity of the brain as well as neuroprotective properties. In this study, we investigated the downstream pathways of NRG1 signalling and their role in the prevention of A(1-42)-induced neurotoxicity.MethodsLactate dehydrogenase (LDH) release, reactive oxygen species (ROS) generation, superoxide dismutase (SOD) activity and TUNEL staining were assayed to examine the neuroprotective properties in primary rat cortical neurons.Key findingsThe inhibition of PI3K/Akt activation abolished the ability of NRG1 to prevent A(1-42)-induced LDH release and increased TUNEL-positive cell count and reactive oxygen species accumulation in primary cortical neurons.ConclusionsOur results demonstrate that NRG1 signalling exerts a neuroprotective effect against A(1-42)-induced neurotoxicity via activation of the PI3K/Akt pathway. Furthermore, this suggests that NRG1 has neuroprotective potential for the treatment of AD.