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Essential Metals in Neurological Diseases and Cancer

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Dear Colleagues,

Alterations to the homeostasis of the essential metals iron (Fe), zinc (Zn), copper (Cu), selenium (Se), manganese (Mn), magnesium (Mg), lithium (Li), and other essential elements could play a role in the most relevant challenges in human health, including cancer and neurological and psychiatric diseases, although their precise mechanisms are still far from been revealed. For instance, in Alzheimer’s disease, Fe and Cu are thought to be drivers of oxidative stress in processes related to ferroptosis and cuproptosis, and they might also eventually contribute to amyloid plaque formation or tau tangles, leading to neuronal cell death. Zn and Li may be protective of neurogenesis and neuronal functions, while the role of the other essential metals is still elusive. Furthermore, Fe-regulated genes and Se are involved in cancer progression. Finally, recent studies reported that metal-based compounds can exert anti-cancer and neuroprotective actions. In order to improve knowledge in the field and prompt further research, the current Special Issue aims to gather the most recent data and information on metal-based mechanisms underlying neurodegeneration and cancer and to detail the chemistry of transition metal complexes or chelating agents targeting these diseases.

Potential topics include, but are not limited to:

Improvements in knowledge of mechanisms of metal toxicity or neuroprotection as well as genetics;
Metal–protein interplay and metals’ potential as biomarkers of stratification or prognosis;
System biology/bioinformatics-based approaches.

Dr. Rosanna Squitti
Guest Editor

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Keywords

neurodegenerative disorders
cancer
essential metals
Alzheimer’s disease
psychiatric disordes
copper
iron
zinc

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Research

19 pages, 4554 KiB

Open AccessArticle

Interplay of Vitamin D, Unfolded Protein Response, and Iron Metabolism in Neuroblastoma Cells: A Therapeutic Approach in Neurodegenerative Conditions

by Gergely Jánosa, Edina Pandur, Ramóna Pap, Adrienn Horváth and Katalin Sipos

Int. J. Mol. Sci. 2023, 24(23), 16883; https://doi.org/10.3390/ijms242316883 - 28 Nov 2023

Viewed by 923

Abstract

Vitamin D3 (VD) is crucial for various cell functions, including gene regulation, antioxidant defense, and neural health. Neurodegenerative conditions are closely linked to the unfolded protein response (UPR), a mechanism reacting to endoplasmic reticulum (ER) stress. Iron metabolism is intricately associated with UPR and neurodegeneration. This study used SH-SY5Y neuroblastoma cells to investigate the relationship between UPR, iron metabolism, and VD. Different sequences of treatments (pre- and post-treatments) were applied using VD and thapsigargin (Tg), and various methods were used for evaluation, including real-time qPCR, Western blotting, ELISA, and iron content analysis. The findings indicate that VD affects UPR pathways, cytokine release, and iron-related genes, potentially offering anti-inflammatory benefits. It also influences iron transporters and storage proteins, helping to maintain cellular iron balance. Furthermore, pro-inflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα) were impacting UPR activation in cells. VD also influenced fractalkine (CX3CL1) gene expression and secretion, suggesting its potential as a therapeutic agent for addressing neuroinflammation and iron dysregulation. This research provides insights into the intricate connections among VD, UPR, and iron metabolism in SH-SY5Y neuroblastoma cells, with implications for future investigations and potential therapeutic approaches in neurodegenerative diseases characterized by UPR dysregulation and iron accumulation. Full article

(This article belongs to the Special Issue Essential Metals in Neurological Diseases and Cancer)

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14 pages, 3286 KiB

Open AccessArticle

The Impact of Hydroxytyrosol on the Metallomic-Profile in an Animal Model of Alzheimer’s Disease

by Miguel Tabanez, Ilma R. Santos, Juliane M. Ikebara, Mariana L. M. Camargo, Bianca A. Dos Santos, Bruna M. Freire, Bruno L. Batista, Silvia H. Takada, Rosanna Squitti, Alexandre H. Kihara and Giselle Cerchiaro

Int. J. Mol. Sci. 2023, 24(19), 14950; https://doi.org/10.3390/ijms241914950 - 06 Oct 2023

Cited by 1 | Viewed by 1101

Abstract

It is undeniable that as people get older, they become progressively more susceptible to neurodegenerative illnesses such as Alzheimer’s disease (AD). Memory loss is a prominent symptom of this condition and can be exacerbated by uneven levels of certain metals. This study used inductively coupled plasma mass spectrometry (ICP-MS) to examine the levels of metals in the blood plasma, frontal cortex, and hippocampus of Wistar rats with AD induced by streptozotocin (STZ). It also tested the effects of the antioxidant hydroxytyrosol (HT) on metal levels. The Barnes maze behavior test was used, and the STZ group showed less certainty and greater distance when exploring the Barnes maze than the control group. The results also indicated that the control group and the STZ + HT group exhibited enhanced learning curves during the Barnes maze training as compared to the STZ group. The ICP-MS analysis showed that the STZ group had lower levels of cobalt in their blood plasma than the control group, while the calcium levels in the frontal cortex of the STZ + HT group were higher than in the control group. The most important finding was that copper levels in the frontal cortex from STZ-treated animals were higher than in the control group, and that the STZ + HT group returned to equivalent levels to the control group. The antioxidant HT can restore copper levels to their basal physiological state. This finding may help explain HT’s potential beneficial effect in AD-patients. Full article

(This article belongs to the Special Issue Essential Metals in Neurological Diseases and Cancer)

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