Excessive Activation of NMDA Receptors in the Pathogenesis of Multiple Peripheral Organs via Mitochondrial Dysfunction,
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MEDICINE
Excessive Activation of NMDA Receptors in the Pathogenesis of Multiple Peripheral Organs via Mitochondrial Dysfunction, Oxidative Stress, and Inflammation Tianqi Ma 1,2 & Qingmei Cheng 3 & Chen Chen 4 & Ziqiang Luo 1 & Dandan Feng 1 Accepted: 16 April 2020 / Published online: 8 May 2020 # Springer Nature Switzerland AG 2020
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 proinflammatory 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. Keywords NMDA receptor . Peripheral organs . Pathology . Mitochondrial dysfunction . Oxidative stress . Inflammation
Introduction Because of the important role glutamate plays in the signal conduction of nervous system, previously, most studies on NMDA receptors (NMDARs) were concentrated on the field of neuroscience and have suggested that NMDAR is important in various physiological activities in central nervous system (CNS) [1–3] and pathophysiological progression of neurodegenerative diseases such as Parkinson’s disease [4], suggesting NMDAR as a therapeutic target in neurological diseases [5]. This article is part of the Topical Collection on Medicine * Dandan Feng [email protected] 1
Department of Physiology, Xiangya School of Medicine, Central South University, Tongzi Slope Road 172#,, Changsha 410013, China
2
Department of Geriatric Medicine, Xiangya Hospital, Central South University, Xiangya Road 87#,, Changsha 410008, China
3
Department of Orthopaedics, Xiangya Hospital, Central South University, Xiangya Road 87#,, Changsha 410008, China
4
School of Biomedical Sciences, University of Queensland, St Lucia, Brisbane, QLD 4072, Australia
Nervous NMDAR’s structure, function, and distribution have been widely clarified. NMDARs also present in peripheral tissues including heart, lung, kidney, retina, bone, and pancreas [6–9], in which NMDAR participates in bone apposition, wound healing, insulin secretion, and other physiological or pathophysiological processes [10]. This review concentrates on the possible role of NMDARs in the pathophysiological process of diseases in lungs, heart, kidneys, and pancreas, where the up-regulation and over-stimulation of the NMDARs contribute to either acute injury or chronic diseases. Meanwhile, the possibility of perip
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