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Advances in Metal Toxicology—a Honorary Special Issue Commemorating the Research of Prof. Michael Aschner in Metal Toxicity

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A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 7219

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Special Issue Editors

Dr. Alexey A. Tinkov

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Guest Editor

Laboratory of Ecobiomonitoring and Quality Control, Yaroslavl State University, Sovetskaya Str. 14, 150000 Yaroslavl, Russia
Interests: trace elements in metabolic syndrome; neurotoxicity; trace element biochemistry
Special Issues, Collections and Topics in MDPI journals

Dr. Anatoly Skalny

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Guest Editor

World-Class Research Center “Digital Biodesign and Personalized Healthcare”, IM Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia
Interests: trace elements in epidemiology; physiology; sport medicine; autism research

Special Issue Information

Dear Colleagues,

The forthcoming year, 2023, marks the 40-year anniversary of acceptance of a manuscript by Prof. Michael Aschner, titled “Persistent, differential alterations in developing cerebellar cortex of male and female mice after methylmercury exposure” (Developmental Brain Research, 1984, 12(1), 1–11.), which opened a new field in metal toxicology. Starting from methylmercury, the research interests of Prof. Aschner expanded to other toxic metals, including manganese, tin, and lead. With a special focus on the brain, Prof. Aschner and his colleagues clearly demonstrated the involvement of neuroinflammation, oxidative stress, endoplasmic stress, mitochondrial dysfunction, cytoskeletal pathology, excitotoxicity, and other alterations of neurotransmitter metabolism in metal neurotoxicity, thus shedding a light on the causal role of metal overload in multiple neurological and especially neurodegenerative diseases, including Parkinson’s disease. The key role of astrocytes in metal neurotoxicity was also demonstrated. As a continuation of the novel ideas of Prof. Aschner in metal toxicology, this Special Issue will focus on a discussion of the molecular mechanisms underlying metal toxicity and the role of metal overload in pathogenesis.

Dr. Alexey A. Tinkov
Dr. Anatoly Skalny
Guest Editors

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. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

metal toxicology
heavy metals
methylmercury
manganese
neurotoxicity

Published Papers (4 papers)

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Research

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17 pages, 2071 KiB

Open AccessArticle

IGF/mTORC1/S6 Signaling Is Potentiated and Prolonged by Acute Loading of Subtoxicological Manganese Ion

by Xueqi Tang, Rekha C. Balachandran, Michael Aschner and Aaron B. Bowman

Biomolecules 2023, 13(8), 1229; https://doi.org/10.3390/biom13081229 - 8 Aug 2023

Viewed by 1112

Abstract

The insulin-like growth factor (IGF)/insulin signaling (IIS) pathway is involved in cellular responses against intracellular divalent manganese ion (Mn²⁺) accumulation. As a pathway where multiple nodes utilize Mn²⁺ as a metallic co-factor, how the IIS signaling patterns are affected by Mn²⁺ overload is unresolved. In our prior studies, acute Mn²⁺ exposure potentiated IIS kinase activity upon physiological-level stimulation, indicated by elevated phosphorylation of protein kinase B (PKB, also known as AKT). AKT phosphorylation is associated with IIS activity; and provides direct signaling transduction input for the mammalian target of rapamycin complex 1 (mTORC1) and its downstream target ribosomal protein S6 (S6). Here, to better define the impact of Mn²⁺ exposure on IIS function, Mn²⁺-induced IIS activation was evaluated with serial concentrations and temporal endpoints. In the wild-type murine striatal neuronal line STHdh, the acute treatment of Mn²⁺ with IGF induced a Mn²⁺ concentration-sensitive phosphorylation of S6 at Ser235/236 to as low as 5 μM extracellular Mn²⁺. This effect required both the essential amino acids and insulin receptor (IR)/IGF receptor (IGFR) signaling input. Similar to simultaneous stimulation of Mn²⁺ and IGF, when a steady-state elevation of Mn²⁺ was established via a 24-h pre-exposure, phosphorylation of S6 also displayed higher sensitivity to sub-cytotoxic Mn²⁺ when compared to AKT phosphorylation at Ser473. This indicates a synergistic effect of sub-cytotoxic Mn²⁺ on IIS and mTORC1 signaling. Furthermore, elevated intracellular Mn²⁺, with both durations, led to a prolonged activation in AKT and S6 upon stimulation. Our data demonstrate that the downstream regulator S6 is a highly sensitive target of elevated Mn²⁺ and is well below the established acute cytotoxicity thresholds (<50 μM). These findings indicate that the IIS/mTORC1 pathways, in which Mn²⁺ normally serves as an essential co-factor, are dually responsible for the cellular changes in exposures to real-world Mn²⁺ concentrations. Full article

(This article belongs to the Special Issue Advances in Metal Toxicology—a Honorary Special Issue Commemorating the Research of Prof. Michael Aschner in Metal Toxicity)

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Review

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22 pages, 1537 KiB

Open AccessReview

Interaction of Heavy Metal Lead with Gut Microbiota: Implications for Autism Spectrum Disorder

by Yousef Tizabi, Samia Bennani, Nacer El Kouhen, Bruk Getachew and Michael Aschner

Biomolecules 2023, 13(10), 1549; https://doi.org/10.3390/biom13101549 - 19 Oct 2023

Cited by 7 | Viewed by 2123

Abstract

Autism Spectrum Disorder (ASD), a neurodevelopmental disorder characterized by persistent deficits in social interaction and communication, manifests in early childhood and is followed by restricted and stereotyped behaviors, interests, or activities in adolescence and adulthood (DSM-V). Although genetics and environmental factors have been implicated, the exact causes of ASD have yet to be fully characterized. New evidence suggests that dysbiosis or perturbation in gut microbiota (GM) and exposure to lead (Pb) may play important roles in ASD etiology. Pb is a toxic heavy metal that has been linked to a wide range of negative health outcomes, including anemia, encephalopathy, gastroenteric diseases, and, more importantly, cognitive and behavioral problems inherent to ASD. Pb exposure can disrupt GM, which is essential for maintaining overall health. GM, consisting of trillions of microorganisms, has been shown to play a crucial role in the development of various physiological and psychological functions. GM interacts with the brain in a bidirectional manner referred to as the “Gut–Brain Axis (GBA)”. In this review, following a general overview of ASD and GM, the interaction of Pb with GM in the context of ASD is emphasized. The potential exploitation of this interaction for therapeutic purposes is also touched upon. Full article

(This article belongs to the Special Issue Advances in Metal Toxicology—a Honorary Special Issue Commemorating the Research of Prof. Michael Aschner in Metal Toxicity)

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14 pages, 581 KiB

Open AccessReview

Manganese-Induced Parkinsonism: Evidence from Epidemiological and Experimental Studies

by Roberto Lucchini and Kim Tieu

Biomolecules 2023, 13(8), 1190; https://doi.org/10.3390/biom13081190 - 30 Jul 2023

Cited by 5 | Viewed by 2103

Abstract

Manganese (Mn) exposure has evolved from acute, high-level exposure causing manganism to low, chronic lifetime exposure. In this latter scenario, the target areas extend beyond the globus pallidus (as seen with manganism) to the entire basal ganglia, including the substantia nigra pars compacta. This change of exposure paradigm has prompted numerous epidemiological investigations of the occurrence of Parkinson’s disease (PD), or parkinsonism, due to the long-term impact of Mn. In parallel, experimental research has focused on the underlying pathogenic mechanisms of Mn and its interactions with genetic susceptibility. In this review, we provide evidence from both types of studies, with the aim to link the epidemiological data with the potential mechanistic interpretation. Full article

(This article belongs to the Special Issue Advances in Metal Toxicology—a Honorary Special Issue Commemorating the Research of Prof. Michael Aschner in Metal Toxicity)

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14 pages, 736 KiB

Open AccessReview

The Role of Oxidative Stress in Manganese Neurotoxicity: A Literature Review Focused on Contributions Made by Professor Michael Aschner

by David C. Dorman

Biomolecules 2023, 13(8), 1176; https://doi.org/10.3390/biom13081176 - 28 Jul 2023

Cited by 3 | Viewed by 1276

Abstract

This literature review focuses on the evidence implicating oxidative stress in the pathogenesis of manganese neurotoxicity. This review is not intended to be a systematic review of the relevant toxicologic literature. Instead, in keeping with the spirit of this special journal issue, this review highlights contributions made by Professor Michael Aschner’s laboratory in this field of study. Over the past two decades, his laboratory has made significant contributions to our scientific understanding of cellular responses that occur both in vitro and in vivo following manganese exposure. These studies have identified molecular targets of manganese toxicity and their respective roles in mitochondrial dysfunction, inflammation, and cytotoxicity. Other studies have focused on the critical role astrocytes play in manganese neurotoxicity. Recent studies from his laboratory have used C. elegans to discover new facets of manganese-induced neurotoxicity. Collectively, his body of work has dramatically advanced the field and presents broader implications beyond metal toxicology. Full article

(This article belongs to the Special Issue Advances in Metal Toxicology—a Honorary Special Issue Commemorating the Research of Prof. Michael Aschner in Metal Toxicity)

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