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Inhibition of PTEN Attenuates Endoplasmic Reticulum Stress and Apoptosis via Activation of PI3K/AKT Pathway in Alzheimer’s Disease

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Abstract

Amyloid plaques and neurofibrillary tangles are pathologic hallmarks of Alzheimer’s disease (AD). Endoplasmic reticulum (ER) stress has been implicated in the loss of neurons in AD. The phosphatase and tensin homolog deleted on chromosome ten (PTEN) plays an important role in regulating neuronal survival processes. However, the direct effects of the PTEN on ER stress and apoptosis in AD have not been elucidated. In this study, we demonstrate that the expression of PTEN and ER stress related proteins, GRP78 and CHOP, increased in APP/PS1 transgenic AD mice compared with WT mice. A PTEN inhibitor, dipotassium bisperoxo-(5-hydroxypyridine-2-carboxyl)-oxovanadate (bpv) could decrease apoptosis, induce AKT phosphorylation and inhibit the ER stress response proteins in hippocampus in APP/PS1 transgenic AD model mice. Furthermore, treatment with the specific PI3K inhibitor, LY294002, significantly blocked the anti-apoptotic effects of bpv in AD mice. The expression in GRP78, CHOP and apoptosis levels by bpv was reversed after PI3K inhibitor treatment. Taken together, our results indicate that the neuroprotective role of bpv involves the suppression of ER stress via the activation of the PI3K/AKT signalling pathways in APP/PS1 transgenic AD model mice.

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Acknowledgements

This study was supported partly by the support project for the Disciplinary group of Psychology and Neuroscience, Xinxiang Medical University (2016PN-KFKT-11), the Henan Key Laboratory of Neural Regeneration and Repairment (HNSJXF-2016-007), key research areas of Xinxiang Medical University (Grant No. ZD2011-28), the Science and Technology Project of Department of Education of Henan Province (Grant No. 13A310862), the National Natural Science Foundation of China (Grant Nos. 81301174, 81260211, 81560236).

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Authors and Affiliations

  1. Henan Key Laboratory of Medical Tissue Regeneration, Department of Human Anatomy, Xinxiang Medical University, Xinxiang, 453003, Henan, China

    Weigang Cui, Songtao Wang, Zhiyong Wang, Chunli Sun & Yinghua Zhang

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

    Zhongping Wang

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  1. Weigang Cui
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  2. Songtao Wang
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  3. Zhongping Wang
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  4. Zhiyong Wang
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  5. Chunli Sun
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Correspondence to Weigang Cui or Yinghua Zhang.

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Cui, W., Wang, S., Wang, Z. et al. Inhibition of PTEN Attenuates Endoplasmic Reticulum Stress and Apoptosis via Activation of PI3K/AKT Pathway in Alzheimer’s Disease. Neurochem Res 42, 3052–3060 (2017). https://doi.org/10.1007/s11064-017-2338-1

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