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Estrogen receptors’ neuroprotective effect against glutamate-induced neurotoxicity

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Abstract

Glutamate is the most abundant excitatory brain neurotransmitter that has important functional significance with respect to neurodegenerative conditions. Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer’s disease (AD) has been gradually becoming elucidated recently. Excessive release of glutamate induces an increase in intracellular Ca2+ levels, thus triggers a cascade of cellular responses, ultimately leading to neuronal cell death. This type of neuronal damage induced by over-excitation has been proposed to be involved in a number of neuropathological conditions, ranging from acute insults to chronic neurodegenerative disorders. Estrogen could be effective in modulating glutamate-induced neurotoxicity and the protective responsivenesses are mostly estrogen receptors (ERs)-dependent. However, the mechanism underlying estrogen’s neuroprotective effect is not fully clarified and is complicated by the presence of several distinct ER types. So a deeper research into the neuroprotection of ERs might be informative about the positive effect that estrogen might have on ageing-related cognitive changes. Extensive studies have indicated the neuroprotective effects of ERs against glutamate-induced neurotoxicity. The purpose of this review is to elucidate ERs’ neuroprotective effects against glutamate-induced cytotoxicity and explore new ways to prevent and cure neurotoxicity-associated neurodegenerative disorders.

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Acknowledgments

The work was supported by the National Natural Science Foundation of China (81371223 and 81371437) and the Research Fund for the Doctoral Program of Higher Education of China (20122105110010).

Conflict of interest

The authors declare that they have no conflict of interest related to the publication of this article.

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Authors and Affiliations

  1. Department of Physiology, Dalian Medical University, Dalian, 116044, China

    Yu-Long Lan, Jie Zhao & Shao Li

  2. Liaoning Engineering Technology Centre of Target-based Nature Products for Prevention and Treatment of Ageing-related Neurodegeneration, Dalian, 116044, China

    Jie Zhao

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  1. Yu-Long Lan
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Correspondence to Jie Zhao or Shao Li.

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Lan, YL., Zhao, J. & Li, S. Estrogen receptors’ neuroprotective effect against glutamate-induced neurotoxicity. Neurol Sci 35, 1657–1662 (2014). https://doi.org/10.1007/s10072-014-1937-8

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  • DOI: https://doi.org/10.1007/s10072-014-1937-8

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