Neurochemical Research

, Volume 38, Issue 11, pp 2237–2246 | Cite as

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

  • Weigang Cui
  • Jing Tao
  • Zhongping Wang
  • Mingxin Ren
  • Yinghua Zhang
  • Yan Sun
  • Yuwen Peng
  • Ruixi Li
Original Paper


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.


Neuregulin1 Apoptosis PI3-kinase/Akt pathway ErbB4 Alzheimer’s disease 



This work was supported by the Science and Technology Project of Department of Education of Henan Province (No. 13A310862), the Key Research Areas of Xinxiang Medical University (No. ZD2011-28, ZD2011-14), the Doctoral Scientific Research Activation Foundation of Xinxiang Medical University, Natural Science Foundation of Jiangxi Province, China (No. 20114BAB205063), and National Natural Science Foundation of China (No. 81260211). We would also like to express thanks to Professors Guomin Zhou and Zulin Chen for introducing the animal model.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Weigang Cui
    • 1
    • 2
  • Jing Tao
    • 1
  • Zhongping Wang
    • 2
    • 3
  • Mingxin Ren
    • 1
  • Yinghua Zhang
    • 1
    • 2
  • Yan Sun
    • 2
  • Yuwen Peng
    • 2
    • 4
  • Ruixi Li
    • 2
    • 4
  1. 1.Key Open Lab for Tissue Regeneration of Henan Universities, Department of Human AnatomyXinxiang Medical UniversityXinxiangChina
  2. 2.Department of Anatomy, Histology and Embryology, Shanghai Medical CollegeFudan UniversityShanghaiChina
  3. 3.Department of Microbiology and Immunology, School of Basic Medical SciencesJiujiang UniversityJiujiangChina
  4. 4.Department of Anatomy, Histology and Embryology, Shanghai Medical SchoolFudan UniversityShanghaiChina

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