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Neuregulin1beta1 Antagonizes Apoptosis Via ErbB4-Dependent Activation of PI3-Kinase/Akt in APP/PS1 Transgenic Mice

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Abstract

Alzheimer’s disease (AD) is characterized by the deposition of beta-amyloid protein (Aβ) and extensive neuronal cell death. Apoptosis plays a crucial role in loss of neurons in AD. Neuregulin1 (NRG1) has been found to protect neurons from oxygen glucose deprivation induced apoptosis and hypoxia ischemia induced apoptosis. However, the relationship between NRG1 and apoptosis related protein expression in AD and its mechanism remain uncertain. The present study explores the effects of NRG1 on Aβ-induced apoptosis in AD. In this study, extracellular domain of NRG1beta1 (NRG1β1-ECD) promoted the expression of p-ErbB4 receptor, p-Akt and increased the level of Bcl-2 both in APP/PS1 transgenic mice and in vitro. In primary culture of neurons, the level of Bcl-2 protein decreased significantly after Aβ treatment. These changes were inhibited by pretreatment of neurons with NRG1β1-ECD. A specific inhibitor of PI3-kinase/Akt pathway, wortmannin, significantly abrogated the effects of NRG1β1-ECD on p-Akt and Bcl-2 levels. Furthermore, the expression of PI3-kinase/Akt by NRG1β1-ECD was ErbB4-dependent. Our data demonstrated that NRG1β1-ECD might serve as an obvious neuroprotection in AD, and the possible protective mechanism occurs most likely via ErbB4-dependent activation of PI3-kinase/Akt pathway.

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Acknowledgments

This work was supported by the Science and Technology Project of Department of Education of Henan Province (No. 13A310862), the Key Research Areas of ** Wang, Yinghua Zhang, Yan Sun, Yuwen Peng & Ruixi Li

  • Department of Microbiology and Immunology, School of Basic Medical Sciences, Jiujiang University, Jiujiang, 332000, China

    Zhong** Wang

  • Department of Anatomy, Histology and Embryology, Shanghai Medical School, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China

    Yuwen Peng & Ruixi Li

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    1. Weigang Cui
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    2. **g Tao
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    3. Zhong** Wang
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    4. Mingxin Ren
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    Correspondence to Yuwen Peng or Ruixi Li.

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    Cui, W., Tao, J., Wang, Z. et al. Neuregulin1beta1 Antagonizes Apoptosis Via ErbB4-Dependent Activation of PI3-Kinase/Akt in APP/PS1 Transgenic Mice. Neurochem Res 38, 2237–2246 (2013). https://doi.org/10.1007/s11064-013-1131-z

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