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Neurotoxicity: Cellular Death Mechanisms in the Pathogenesis of Neurodegenerative Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 30 November 2026 | Viewed by 2464

Special Issue Editors


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Guest Editor
School of Health Sciences, Purdue University, West Lafayette, IN 47907, USA
Interests: neuropharmacology; receptors; neurodegenerative diseases; neurotoxicology

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Guest Editor

Special Issue Information

Dear Colleagues,

Neurotoxicity resulting in adverse effects on the nervous system and neurological function is a serious public health concern. This complex area of research presents significant challenges for scientists in both neuroscience and toxicology. Growing evidence suggests a strong link between neurotoxicity and the development of neurodegenerative diseases, which generally lack effective treatments. Thus, understanding the intricate mechanisms behind neurotoxicity is essential for identifying and addressing the pathways involved in neurodegeneration.

This Special Issue aims at underscoring neurotoxicity as a critical factor in the progression of neurodegenerative diseases, such as Parkinson’s and Alzheimer’s diseases. We invite submissions that provide innovative insights into the molecular mechanisms connecting toxic exposure to the onset and advancement of these conditions. Special attention will be given to potential therapeutic targets related to neurotoxicity, including ferroptosis—a regulated form of cell death caused by uncontrolled phospholipid peroxidation—and mitochondrial dysfunction, which are vital for mediating neurodegeneration. Furthermore, we encourage manuscripts that explore neuroprotective strategies designed to mitigate the harmful effects of neurotoxicity, thereby enhancing resilience against neurodegeneration.

Dr. Mohammed Jakaria
Prof. Dr. Jason Cannon
Guest Editors

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Keywords

  • neurotoxicity
  • cellular stress
  • neuronal cell death
  • ferroptosis
  • neurodegeneration
  • neuroprotection

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Published Papers (2 papers)

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Research

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12 pages, 1647 KB  
Article
Cytoprotective Mechanism of Necrox-5 Against Toxicity Induced by Experimental Ferroptosis Instigators and the Pesticide Propargite
by Md. Jakaria and Jason R. Cannon
Int. J. Mol. Sci. 2026, 27(4), 1772; https://doi.org/10.3390/ijms27041772 - 12 Feb 2026
Viewed by 661
Abstract
Necrox-5 is an indole-derived antioxidant that inhibits necrotic cell death, likely through prevention of mitochondrial stress, oxidative stress, inflammation, and hypoxia/reoxygenation. However, its protective role against ferroptotic toxicity has not yet been studied. In this study, we induced ferroptosis in HT-22 cells, an [...] Read more.
Necrox-5 is an indole-derived antioxidant that inhibits necrotic cell death, likely through prevention of mitochondrial stress, oxidative stress, inflammation, and hypoxia/reoxygenation. However, its protective role against ferroptotic toxicity has not yet been studied. In this study, we induced ferroptosis in HT-22 cells, an immortalized hippocampal neuronal cell line, using ferroptosis-inducing agents. We also tested Necrox-5 against toxicity induced by propargite, a pesticide known to inhibit complex V (mitochondrial adenosine triphosphate [ATP] synthase) and induce necrosis. We evaluated cytotoxicity using calcein AM and lactate dehydrogenase (LDH) release assays. Additionally, we conducted intracellular and cell-free C11-BODIPY assays to assess the efficacy of Necrox-5 in inhibiting lipid peroxidation. Intracellular glutathione (GSH) levels were measured using the mBCI-GSH assay, while ATP levels were determined through bioluminescence assays. Our findings show that Necrox-5 is a potent inhibitor of ferroptosis induced by erastin, RSL3, FINO2, and iron plus arachidonic acid. Furthermore, we demonstrated that Necrox-5 protects against ferroptosis-like propargite toxicity, although it did not prevent propargite-induced depletion of GSH and ATP. We identified radical-scavenging antioxidant activity as the primary mechanism by which Necrox-5 protects from ferroptosis and propargite toxicity. In conclusion, Necrox-5 is a potent cytoprotective compound that warrants further study for its potential role in ferroptosis-associated complications such as neurodegenerative diseases. Full article
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Review

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33 pages, 1247 KB  
Review
Neurotrophin System Alterations Associated with Neurotoxicity Accompanied by Carotid Artery Diseases—A Systematic Review
by Jovan Milosavljevic, Marina Mitrovic, Dragica Selakovic, Davor Kumburovic, Miodrag Sreckovic, Suzana Randjelovic, Sara Rosic, Miljan Cpajak, Nemanja Jovicic and Gvozden Rosic
Int. J. Mol. Sci. 2026, 27(6), 2817; https://doi.org/10.3390/ijms27062817 - 20 Mar 2026
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Abstract
According to neuropsychiatric sequelae for cardiovascular pathology, carotid artery disease (CAD) represents a significant medical, social, and economic burden. Numerous efforts have been made to define reliable markers that can reflect the principal pathological event and the effect of employed therapeutic protocols, prognoses, [...] Read more.
According to neuropsychiatric sequelae for cardiovascular pathology, carotid artery disease (CAD) represents a significant medical, social, and economic burden. Numerous efforts have been made to define reliable markers that can reflect the principal pathological event and the effect of employed therapeutic protocols, prognoses, and clinical outcomes of CAD. However, the potential role of the neurotrophin (NT) system has not yet been confirmed. This narrative review was conducted following a literature search of PubMed, which included all studies on NT system elements and CAD published over the last two decades, encompassing both animal and clinical investigations, regarding the potential use of NT system elements as biomarkers for neurotoxicity manifestations and therapeutic effectiveness in CAD. Still, the analysis presented in this review is not sufficient to reveal whether NT system elements can be considered as exploratory or standard biomarkers for the evaluation of CAD. Further research is essential to elucidate this dilemma. Full article
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