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Essential Metals in Neurological Diseases and Cancer
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Essential Metals in Neurological Diseases and Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 4630

Special Issue Editor

Dr. Rosanna Squitti

E-Mail Website
Guest Editor
Dipartimento di Scienze di Laboratorio, Sezione Ricerca e Sviluppo, Ospedale Fatebenefratelli Isola Tiberina–Gemelli Isola, Via di Ponte Quattro Capi 39, 00186 Roma, Italy
Interests: neurodegenerative disorders; cancer; essential metals; Alzheimer’s disease; psychiatric disorders; copper; iron; zinc
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neurodegenerative disorders

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

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Published Papers (3 papers)

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Research

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19 pages, 4554 KiB  
Article
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
Cited by 2 | Viewed by 1425
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 [...] Read more.
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  
Article
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 - 6 Oct 2023
Cited by 3 | Viewed by 1647
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 [...] Read more.
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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Review

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17 pages, 884 KiB  
Review
The Role of Copper Overload in Modulating Neuropsychiatric Symptoms
by Mirko Manchia, Pasquale Paribello, Martina Pinna and Gavino Faa
Int. J. Mol. Sci. 2024, 25(12), 6487; https://doi.org/10.3390/ijms25126487 - 12 Jun 2024
Viewed by 1131
Abstract
Copper is a transition metal essential for growth and development and indispensable for eukaryotic life. This metal is essential to neuronal function: its deficiency, as well as its overload have been associated with multiple neurodegenerative disorders such as Alzheimer’s disease and Wilson’s disease [...] Read more.
Copper is a transition metal essential for growth and development and indispensable for eukaryotic life. This metal is essential to neuronal function: its deficiency, as well as its overload have been associated with multiple neurodegenerative disorders such as Alzheimer’s disease and Wilson’s disease and psychiatric conditions such as schizophrenia, bipolar disorder, and major depressive disorders. Copper plays a fundamental role in the development and function of the human Central Nervous System (CNS), being a cofactor of multiple enzymes that play a key role in physiology during development. In this context, we thought it would be timely to summarize data on alterations in the metabolism of copper at the CNS level that might influence the development of neuropsychiatric symptoms. We present a non-systematic review with the study selection based on the authors’ judgement to offer the reader a perspective on the most significant elements of neuropsychiatric symptoms in Wilson’s disease. We highlight that Wilson’s disease is characterized by marked heterogeneity in clinical presentation among patients with the same mutation. This should motivate more research efforts to disentangle the role of environmental factors in modulating the expression of genetic predisposition to this disorder. Full article
(This article belongs to the Special Issue Essential Metals in Neurological Diseases and Cancer)
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