Molecular Signaling Pathways Associated with Neurotoxicity

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cells of the Nervous System".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 3017

Special Issue Editors

Albert Einstein College of Medicine, Yeshiva University, New York, NY, USA
Interests: neurotoxicity; neurological disorders; metals; natural small molecules; C. elegans

E-Mail Website
Guest Editor
Graduation Program in Biochemistry, Universidade Federal do Pampa, Uruguaiana, Brazil
Interests: neurotoxicity; metals; pesticides; nanotoxicology; Caenorhabditis elegans
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Vanderbilt University Medical Center, Nashville, TN, USA
Interests: neurotoxicology; pesticides; metals; human-induced pluripotent stem cell models; microfluidic tissue chips

Special Issue Information

Dear Colleagues,

The rising incidence of neurodegenerative diseases and neurodevelopmental disorders is associated with an increasing social and financial global burden. The cause of neurodegenerative and neurodevelopmental disease is generally difficult to pinpoint, and they are largely due to a combination of genetic and environmental factors. Exposures to neurotoxicants, such as pesticides and heavy metals, are known to negatively impact the human CNS and have been implicated in the pathogenesis of CNS disease. Common molecular mechanisms of neurotoxicity, including oxidative stress, mitochondrial dysfunction and the alteration of protein homeostasis, are regulated via intracellular signaling transduction. Neurotoxicant-induced changes in signaling pathways may interfere with neural circuitry, the CNS immune system and/or blood–brain barrier function, eventually leading to neurological disorders. A considerable challenge to understanding the mechanistic basis of neurotoxicity is the lack of known molecular targets and/or the mechanism by which environmental toxicants affects these targets. Thus, there is an urgent need to investigate mechanistically relevant signaling pathways associated with the ever-growing number and levels of neurotoxicants in our environment. Therefore, we invite our colleagues in the field of neurotoxicology to submit either primary research findings or a review to this Special Issue, entitled “Molecular Signaling Pathways Associated With Neurotoxicity”.

Dr. Pan Chen
Prof. Dr. Daiana Silva Ávila
Dr. M. Diana Neely
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. Cells is an international peer-reviewed open access semimonthly 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

  • neurotoxicity
  • signal transduction
  • heavy metals
  • environmental toxicants
  • neurodegeneration

Published Papers (2 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Review

21 pages, 726 KiB  
Review
Signaling Pathways Involved in Manganese-Induced Neurotoxicity
by Hong Cheng, Beatriz Ferrer Villahoz, Romina Deza Ponzio, Michael Aschner and Pan Chen
Cells 2023, 12(24), 2842; https://doi.org/10.3390/cells12242842 - 14 Dec 2023
Viewed by 1277
Abstract
Manganese (Mn) is an essential trace element, but insufficient or excessive bodily amounts can induce neurotoxicity. Mn can directly increase neuronal insulin and activate insulin-like growth factor (IGF) receptors. As an important cofactor, Mn regulates signaling pathways involved in various enzymes. The IGF [...] Read more.
Manganese (Mn) is an essential trace element, but insufficient or excessive bodily amounts can induce neurotoxicity. Mn can directly increase neuronal insulin and activate insulin-like growth factor (IGF) receptors. As an important cofactor, Mn regulates signaling pathways involved in various enzymes. The IGF signaling pathway plays a protective role in the neurotoxicity of Mn, reducing apoptosis in neurons and motor deficits by regulating its downstream protein kinase B (Akt), mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR). In recent years, some new mechanisms related to neuroinflammation have been shown to also play an important role in Mn-induced neurotoxicity. For example, DNA-sensing receptor cyclic GMP–AMP synthase (cCAS) and its downstream signal efficient interferon gene stimulator (STING), NOD-like receptor family pyrin domain containing 3(NLRP3)-pro-caspase1, cleaves to the active form capase1 (CASP1), nuclear factor κB (NF-κB), sirtuin (SIRT), and Janus kinase (JAK) and signal transducers and activators of the transcription (STAT) signaling pathway. Moreover, autophagy, as an important downstream protein degradation pathway, determines the fate of neurons and is regulated by these upstream signals. Interestingly, the role of autophagy in Mn-induced neurotoxicity is bidirectional. This review summarizes the molecular signaling pathways of Mn-induced neurotoxicity, providing insight for further understanding of the mechanisms of Mn. Full article
(This article belongs to the Special Issue Molecular Signaling Pathways Associated with Neurotoxicity)
Show Figures

Figure 1

34 pages, 2800 KiB  
Review
Mechanisms Associated with Cognitive and Behavioral Impairment Induced by Arsenic Exposure
by Gustavo Ignacio Vázquez Cervantes, Dinora Fabiola González Esquivel, Daniela Ramírez Ortega, Tonali Blanco Ayala, Lucio Antonio Ramos Chávez, Humberto Emanuel López-López, Alelí Salazar, Itamar Flores, Benjamín Pineda, Saúl Gómez-Manzo and Verónica Pérez de la Cruz
Cells 2023, 12(21), 2537; https://doi.org/10.3390/cells12212537 - 28 Oct 2023
Cited by 2 | Viewed by 1345
Abstract
Arsenic (As) is a metalloid naturally present in the environment, in food, water, soil, and air; however, its chronic exposure, even with low doses, represents a public health concern. For a long time, As was used as a pigment, pesticide, wood preservative, and [...] Read more.
Arsenic (As) is a metalloid naturally present in the environment, in food, water, soil, and air; however, its chronic exposure, even with low doses, represents a public health concern. For a long time, As was used as a pigment, pesticide, wood preservative, and for medical applications; its industrial use has recently decreased or has been discontinued due to its toxicity. Due to its versatile applications and distribution, there is a wide spectrum of human As exposure sources, mainly contaminated drinking water. The fact that As is present in drinking water implies chronic human exposure to this metalloid; it has become a worldwide health problem, since over 200 million people live where As levels exceed safe ranges. Many health problems have been associated with As chronic exposure including cancer, cardiovascular diseases, gastrointestinal disturbances, and brain dysfunctions. Because As can cross the blood–brain barrier (BBB), the brain represents a target organ where this metalloid can exert its long-term toxic effects. Many mechanisms of As neurotoxicity have been described: oxidative stress, inflammation, DNA damage, and mitochondrial dysfunction; all of them can converge, thus leading to impaired cellular functions, cell death, and in consequence, long-term detrimental effects. Here, we provide a current overview of As toxicity and integrated the global mechanisms involved in cognitive and behavioral impairment induced by As exposure show experimental strategies against its neurotoxicity. Full article
(This article belongs to the Special Issue Molecular Signaling Pathways Associated with Neurotoxicity)
Show Figures

Graphical abstract

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: p38- and ERK-MAPK signalling modulate developmental neurotoxicity of nickel and vanadium in the Caenorhabditis elegans model
Authors: Omamuyovwi M. Ijomone; Ann-Kathrin Weishaupt; Vivien Michaelis; Julia Bornhorst
Affiliation: Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Wuppertal, Germany
Abstract: Nickel (Ni) and vanadium (V) are characteristic heavy metal constituents of many crude oil blends in Sub-Saharan Africa, and we have previously demonstrated their neurotoxic impact. However, molecular mechanisms driving Ni and V neurotoxicity are still being elucidated. The p38- and ERKs-MAPK pathways, which are mostly known for their involvement in human immune and inflammatory signalling, have been shown to influence an array of neurodevelopmental processes. In the present study, we attempt to elucidate the role of p38- and ERK-MAPK in neurotoxicity after early life exposures to Ni and V using the Caenorhabditis elegans model. Synchronized larvae stage-1 (L1) worms were treated with varying concentrations of Ni and V singly or in combination for 1 hour. Our results show Ni induces lethality in C. elegans even at very low concentrations, while much higher V concentrations are required to induce lethality. Furthermore, we identified that loss-of-function of pmk-1 and pmk-3 which are both homologous to human p38-α (MAPK14) are differentially affected by Ni and V exposures. Also, all exposure scenarios triggered significant developmental delays in both wild-type and mutant strains. We also see increased mitochondrial-derived reactive oxygen species following Ni and V exposures in wild-type worms with differential responses in the mutant strains. Additionally, we observed alterations in dopamine and serotonin levels after metal exposures, particularly in the pmk-1 strain. Overall, our results suggest the p38- and ERK-MAPK signalling pathways may modulate Ni and V neurodevelopmental toxicity potentially affecting mitochondrial health, metal bioavailability and neurotransmitter levels.

Back to TopTop