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.
Highlights
Iron is an important cofactor in many proteins such as heme-containing proteins and iron-containing enzymes
Results revealed that activation of N-methyl-D-aspartate receptors (NMDARs) significantly promoted Fe2+ entry into cells (Cheah et al, 2006)
An investigation with interest to the involvement of NMDARs in non-Tf bound iron (NTBI) influx pathways showed that activation of NMDARs significantly promoted Fe2+ entry into cells using fluorescence-based single cell analysis in rat hippocampal primary cultures (Pelizzoni et al, 2011)
Summary
Iron is an important cofactor in many proteins such as heme-containing proteins and iron-containing enzymes. Crosstalk between NMDARs and Iron of the respective first exon to exon 2 and C-terminus splice variants (+iron-responsive element (IRE), −IRE) due to alternative splice mechanisms (Hubert and Hentze, 2002). Increased import, decreased export or redistribution of intracellular iron might be responsible for iron metabolism disturbance in these diseases, which may increase the vulnerability of neurons to iron. Appropriate activation of NMDARs plays a critical role in physiological functions such as excitatory neurotransmission, synaptic plasticity (Carvajal et al, 2016). We described the advanced knowledge on interaction of iron and NMDARs activation. This will provide implications for understanding pathology of these neurological diseases
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