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Excessive Activation of NMDA Receptors in the Pathogenesis of Multiple Peripheral Organs via Mitochondrial Dysfunction, Oxidative Stress, and Inflammation

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Abstract

It has been well-acknowledged that N-methyl-D-aspartate receptors (NMDARs) in central nervous system play an important role in both physiological functions of neurons and the pathophysiological progression of various neurodegenerative diseases. Besides, the receptors have also been found to present extensively in peripheral organs, such as lungs, kidneys, heart, and pancreas. Under various pathological conditions, peripheral NMDARs are upregulated and excessively activated, initiating calcium influx and intracellular calcium overloading. Subsequently, mitochondrial dysfunction, oxidative stress, and pro-inflammatory signaling pathway activation ultimately aggravate tissue damage and organ dysfunction. In addition, excessive activation of NMDARs also directly initiates mitochondrial apoptosis in many organs. Here, we discuss pathophysiological roles of NMDARs in cardiovascular system, lungs, kidneys, and pancreas.

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Acknowledgements

We would like to thank Cheng Haipeng, Lan Jinrong, Fang Lijuan, Cao Yuanyuan, Li Yanghang, Luo Yongyu, Bao Xingwen, Hua Qingzhong, Liang Xinyue, and Qiu Yujia for their perpetual support and encouragement.

Funding

This study was funded by the National Natural Science Foundation of China (Grants 81170717, 81570065, 81870059).

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Authors and Affiliations

  1. Department of Physiology, Xiangya School of Medicine, Central South University, Tongzi Slope Road 172#,, Changsha, 410013, China

    Tianqi Ma, Ziqiang Luo & Dandan Feng

  2. Department of Geriatric Medicine, Xiangya Hospital, Central South University, Xiangya Road 87#,, Changsha, 410008, China

    Tianqi Ma

  3. Department of Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87#,, Changsha, 410008, China

    Qingmei Cheng

  4. School of Biomedical Sciences, University of Queensland, St Lucia, Brisbane, QLD, 4072, Australia

    Chen Chen

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  1. Tianqi Ma
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Contributions

Feng Dandan and Ma Tianqi developed the conception of the work, Ma Tianqi drafted the manuscript, Cheng Qingmei contributed to the organization of tables and figures, Luo Ziqiang, Feng Dandan, and Chen Chen ensured that questions related to the accuracy or integrity of the work are appropriately investigated and resolved, and the authors were responsible for the final version of the manuscript.

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Correspondence to Dandan Feng.

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Ma, T., Cheng, Q., Chen, C. et al. Excessive Activation of NMDA Receptors in the Pathogenesis of Multiple Peripheral Organs via Mitochondrial Dysfunction, Oxidative Stress, and Inflammation. SN Compr. Clin. Med. 2, 551–569 (2020). https://doi.org/10.1007/s42399-020-00298-w

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