Expression of RNAs Coding for Metal Transporters in Blood of Patients with Huntington’s Disease

Abstract

Recent studies have demonstrated elevated levels of iron (Fe) in brains of patients with Huntington’s disease (HD). Striatal cells carrying mutated Huntingtin presented increased sensitivity to cadmium (Cd) toxicity, decreased sensitivity to manganese (Mn) toxicity and deficits in Mn uptake. The hypothesis arose that the observed alterations result from the altered expression and/or activity of proteins engaged in the transport of these metals, that is: transferrin (TF), transferrin receptor (TFR), divalent metal transporter 1 (DMT1) and ZIP8 protein. Here we examined the expression levels of genes encoding these proteins in blood of HD patients and control subjects. A decreasing tendency in the level of TF transcript and increasing tendency of SLC11A2 mRNA encoding DMT1 was observed in the blood of HD patients compared to the control subjects, but neither attained statistical significance. No changes were found in the levels of TFRC coding for TFR and SLC39A8 coding for ZIP8 between HD patients and controls. The results indicate that HD-associated changes in metal homeostasis occur are not related to mechanisms other than the expression level of the here analyzed metal transporters.

The Dual Role of Hepcidin in Brain Iron Load and Inflammation

“…In other diseases accompanied with neurodegeneration (Huntington disease, amyotrophic lateral sclerosis) iron deposition is also increased in different brain structures ( Chen et al, 2013 ; Muller and Leavitt, 2014 ; Szeliga et al, 2016 ; Moreau et al, 2018 ). Changes in expression of iron protein carriers and the therapeutic potential of iron chelation evoke striking similarities with AD and PD ( Salazar et al, 2008 ; Zheng et al, 2009 ; Chen et al, 2013 ; Belaidi and Bush, 2016 ; Szeliga et al, 2016 ; Moreau et al, 2018 ). It is speculative to suggest that the role of hepcidin in neurodegenerative diseases might be of primary importance, due to the dominating role of innate immune system in the pathophysiology of these diseases.…”

A Novel Huntington’s Disease Assessment Platform to Support Future Drug Discovery and Development

“…The SLC2A family of glucose transporters was also strongly implicated in HD, with GLUT1 ( SLC2A1 ) and GLUT3 ( SLC2A3 ) expression shown to be 3- and 4-fold decreased in late stage patients [ 152 ], while an increase in GLUT4 ( SLC2A4 ) expression was seen in a different study [ 153 ]. Other SLCs with increased expression in humans in association with HD were divalent metal transporter 1 (DMT1, SLC11A2 ; although not statistically significant) [ 154 ], equilibrative nucleoside transporter 1 (ENT1, SLC29A1 ) [ 155 ], monocarboxylate transporter 9 (MCT9, SLC16A9 ) [ 142 ], prostein ( SLC45A3 ) [ 156 ], and urea transporter 1 (UT1, SLC14A1 ) [ 142 ]. Other SLCs that have been associated with HD in different ways are bicarbonate transporter-related protein 1 (BTR1, SLC4A11 ) [ 157 ], sodium-hydrogen exchanger 1 (NHE1, SLC9A1 ) [ 158 ], organic cation/carnitine transporter 2 (OCTN2, SLC22A5 ) [ 159 ], phosphate carrier protein (PHC, SLC25A3 ) [ 160 ], SLC3A2 [ 160 ], sodium-dependent vitamin c transporter 2 (SVCT2, SLC23A2 ) [ 161 ], and zinc transporter 10 (ZnT10, SLC30A10 ) [ 162 ].…”