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Neuroglobin Attenuates Beta Amyloid-Induced Apoptosis Through Inhibiting Caspases Activity by Activating PI3K/Akt Signaling Pathway

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Abstract

Excessive accumulation and deposition of amyloid-beta (Aβ) has been considered as a pivotal event in the pathogenesis of Alzheimer’s disease (AD). Neuronal apoptosis is one of the characteristics of AD, which is a possible mechanism underlying Aβ-induced neuronal neurotoxicity. Neuroglobin (Ngb) is a newly discovered vertebrate heme protein that exhibits neuroprotective functions against cell death associated with hypoxic and amyloid insult. However, until now, the exact mechanism of neuroglobin’s protective action has not been determined. To investigate the potential neuroprotective roles and mechanisms of Ngb, transgenic AD mice (APPswe/PSEN1dE9) and SH-SY5Y cells transfected with pAPPswe were enrolled into the study. In vivo, overexpression of Ngb via intracerebroventricular injection with pNgb attenuated memory, cognitive impairment, and plaque generations. In pAPPswe transfected SH-SY5Y cells, Ngb not only decreased the generation of Aβ42, but also attenuated mitochondrial dysfunction and apoptosis through suppressing the activation of caspase-3, caspase-9 by Akt activating phosphorylation, which were restrained by phosphatidylinositol 3-kinase inhibitor (LY294002). Our data indicate the anti-apoptotic property of Ngb may play a neuroprotective role against AD.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (NSFC: 81100948; NSFC: 81271426). We thank Deng Yu and Lin Xiao for their expert technical assistance in cell culture and immunocytochemistry.

Conflicts of Interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Pathology, Chongqing Medical University, Chongqing, China

    Yu Li, Jie-yun Sun, Yue Xiang, Jun Yang, Song-yang Dai & Xiong Zhang

  2. Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, China

    Yu Li, Jie-yun Sun, Yue Xiang, Jun Yang, Song-yang Dai & Xiong Zhang

  3. Institute of Neuroscience & Key Laboratory of Neurobiology, Chongqing Medical University, No. 1 Yixueyuan Road, Yuzhong District, 400016, Chongqing, China

    Yu Li, Jie-yun Sun, Yue Xiang, Jun Yang, Song-yang Dai & Xiong Zhang

  4. Department of Otolaryngology, Guizhou Provincial People’s Hospital, Guiyang, China

    Yu-bing Dai

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  1. Yu Li
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Correspondence to Xiong Zhang.

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Li, Y., Dai, Yb., Sun, Jy. et al. Neuroglobin Attenuates Beta Amyloid-Induced Apoptosis Through Inhibiting Caspases Activity by Activating PI3K/Akt Signaling Pathway. J Mol Neurosci 58, 28–38 (2016). https://doi.org/10.1007/s12031-015-0645-z

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  • DOI: https://doi.org/10.1007/s12031-015-0645-z

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