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New Insights into the Crosstalk between NMDARs and Iron: Implications for Understanding Pathology of Neurological
Huamin Xu1, Hong Jiang1, Junxia Xie1
1Collaborative Innovation Center for Brain Science, Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, Medical College of Qingdao UniversityQingdao, China; Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Qingdao UniversityQingdao, China.
Abstract:
Both iron dyshomeostasis and N-methyl-D-aspartate receptors (NMDARs)-mediated neurotoxicity have been shown to have an important role in neurological diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD). Evidence proved that activation of NMDARs could promote iron overload and iron-induced neurotoxicity by enhancing iron importer divalent metal transporter 1 (DMT1)-mediated iron uptake and iron releasing from lysosome. Also, iron overload could regulate NMDARs-mediated synaptic transmission. This indicates that there might be a possible relationship between iron and activation of NMDARs in neurological diseases. Understanding this interaction between iron and activation of NMDARs may provide new therapeutic avenues for a more targeted neurotherapeutic strategy for these diseases. Therefore, in this review article, we will describe the dysfunction of iron metabolism and NMDARs in neurological diseases including PD and AD, and summarize the new insight into the mechanisms underlying the interaction between iron and activation of NMDARs.