Inhibition of Oxidative Stress and Related Signaling Pathways in Neuroprotection—3rd Edition

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Health Outcomes of Antioxidants and Oxidative Stress".

Deadline for manuscript submissions: 31 December 2026 | Viewed by 2397

Special Issue Editors


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Guest Editor
1. Division of Molecular Medicine, Rudjer Boskovic Institute, 10000 Zagreb, Croatia
2. School of Medicine, Catholic University of Croatia, 10000 Zagreb, Croatia
Interests: neuroprotection; neurotoxicity; neurodegenerative diseases; oxidative stress; polyphenols; neuropharmacology
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Special Issue Information

Dear Colleagues,

Following the success of our previous editions, we are pleased to announce the third edition of this Special Issue, “Inhibition of Oxidative Stress and Related Signaling Pathways in Neuroprotection—3rd Edition.” This Special Issue continues to focus on compounds with antioxidative properties and their ability to attenuate oxidative stress, modulate redox-sensitive signaling pathways, and promote neuronal survival.

Oxidative stress is a key contributor to neuronal dysfunction and degeneration in various neurological diseases. Considerable progress has been made in understanding how antioxidative agents influence intracellular pathways involved in oxidative injury, such as the Nrf2/ARE pathway, MAPK signaling (ERK, JNK, p38), NF-κB activity, mitochondrial pathways, and mechanisms regulating apoptosis and autophagy. Nevertheless, important questions remain about how different compounds, both natural and synthetic, interact with these pathways and restore redox balance under diverse cellular conditions.

We also welcome studies that shed light on cellular conditions (such as metal dyshomeostasis) in which traditionally antioxidative compounds may exhibit prooxidative effects, ultimately influencing neuronal survival.  Such insights can provide valuable context for interpreting compound-specific actions and understanding their full range of biological activities. These contributions will support ongoing efforts to advance therapeutic strategies for neuroprotection.

We look forward to your valuable contributions to this Special Issue.

Dr. Maja Jazvinšćak Jembrek
Dr. Josipa Vlainić
Guest Editors

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Keywords

  • neuroprotection
  • neurotoxicity
  • antioxidative vs. prooxidative activity
  • antioxidant capacity
  • signaling pathways
  • redox metals
  • apoptosis
  • ferroptosis
  • cuproptosis
  • autophagy

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Published Papers (2 papers)

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Research

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28 pages, 7388 KB  
Article
Isoliquiritigenin, a Bioactive Blood Component Derived from Licorice, Activates Nrf2 Enzymes to Confer Protection Against Radiation-Induced Nerve Injury
by Juan Yao, Jiaqi Ma, Huanhuan Lin, Changxin Shao, Xuefeng Liu and Xiaojie Jin
Antioxidants 2026, 15(5), 614; https://doi.org/10.3390/antiox15050614 - 13 May 2026
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Abstract
Licorice is a traditional Chinese medicine; however, its bioactive constituents and specific molecular mechanisms responsible for protecting against radiation-induced brain injury remain poorly elucidated. Oxidative stress overactivation acts as the core pathological mechanism underlying radiation-triggered neuronal injury. This study aimed to investigate the [...] Read more.
Licorice is a traditional Chinese medicine; however, its bioactive constituents and specific molecular mechanisms responsible for protecting against radiation-induced brain injury remain poorly elucidated. Oxidative stress overactivation acts as the core pathological mechanism underlying radiation-triggered neuronal injury. This study aimed to investigate the neuroprotective effect and underlying mechanism of isoliquiritigenin (ISL), a major blood-absorbed component of licorice, against radiation-induced neural injury in C57BL/6J mice via the Keap1-Nrf2 signaling pathway. Molecular docking and MST analysis verified the strong binding affinity of ISL to Keap1. In vitro, ISL restored the viability of X-ray-irradiated PC12 cells; reduced LDH release and intracellular ROS accumulation; and enhanced SOD1 activity, GSH content, and T-AOC levels. Moreover, ISL upregulated the expression of antioxidant-related genes and induced Nrf2 nuclear translocation. In vivo, oral ISL administration ameliorated radiation-induced cognitive impairment, improved spatial learning and memory, alleviated hippocampal neuronal loss, and increased cerebral cortical Nrf2 expression in C57BL/6J mice. In conclusion, ISL alleviates radiation-induced neuronal injury by suppressing oxidative stress and activating the Keap1-Nrf2 signaling pathway, thus representing a promising therapeutic agent for the prevention and treatment of radiation brain injury. Full article
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Review

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58 pages, 3432 KB  
Review
Receptor–Mitochondria Crosstalk in the Kynurenine Metabolic Pathway: Integrating Metabolomics and Clinical Mass Spectrometry
by László Juhász, Zsolt Galla, Masaru Tanaka and László Vécsei
Antioxidants 2026, 15(2), 261; https://doi.org/10.3390/antiox15020261 - 19 Feb 2026
Cited by 1 | Viewed by 1716
Abstract
Mitochondria govern energy transfer, redox balance, and cell fate. Tryptophan catabolism generates kynurenines (KYNs) that can tune mitochondrial function, with growing evidence that G protein-coupled receptor 35 (GPR35), aryl hydrocarbon receptor (AhR), and N-methyl-D-aspartate receptors (NMDA receptors) link extracellular cues to adenosine 5 [...] Read more.
Mitochondria govern energy transfer, redox balance, and cell fate. Tryptophan catabolism generates kynurenines (KYNs) that can tune mitochondrial function, with growing evidence that G protein-coupled receptor 35 (GPR35), aryl hydrocarbon receptor (AhR), and N-methyl-D-aspartate receptors (NMDA receptors) link extracellular cues to adenosine 5 prime triphosphate (ATP) maintenance, calcium (Ca2+) handling, mitophagy, and inflammasome control. In parallel, quinolinic acid (QA)-driven de novo nicotinamide adenine dinucleotide (NAD+) synthesis connects KYN flux to tricarboxylic acid (TCA) cycle activity and sirtuin programs across tissues. Key gaps remain: receptor pharmacology is rarely integrated with NAD+ economics and respiration, and clinical workflows still lack single-run assays that quantify both kynurenine and TCA nodes. We therefore integrate receptor proximal signaling, QA-driven NAD+ supply, and unified liquid chromatography–mass spectrometry (LC-MS) measurement into one translational framework spanning kynurenic acid (KYNA), KYN, 3-hydroxykynurenine (3-HK), and QA, using mitochondrial endpoints as the common readout. We synthesize evidence for mitochondrial GPR35 signaling that preserves ATP, AhR programs that tune oxidative defenses and mitophagy, and NMDA receptor antagonism that limits excitotoxic stress. These mechanisms are linked to QA-dependent NAD+ biogenesis and alpha ketoglutarate control points, then aligned with chromatography and ionization choices suited to routine LC-MS workflows. This receptor to organelle framework couples KYN flux to respiratory control and provides a practical roadmap for standardized single-run LC-MS panels. It can strengthen target validation in ischemia, neurodegeneration, psychiatry, and oncology while improving biomarker qualification through harmonized analytics and decision-grade readouts. Full article
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