Innovative Approaches to Neuroprotective Strategies: Targeting Oxidative Stress in Neurodegenerative Disorders

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: 28 February 2026 | Viewed by 1185

Special Issue Editor


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Guest Editor
Department of Molecular Neurochemistry, Medical University of Lodz, 92215 Lodz, Poland
Interests: neurochemistry; neurobiology; neurodegeneration; neuroprotection; signaling pathway; cAMP/PKA signaling

Special Issue Information

Dear Colleagues,

Oxidative stress, defined as an imbalance between the production of reactive oxygen species (ROS) and the capacity of antioxidant defense systems, plays a central role in the onset and progression of neurodegenerative diseases. Neurons are particularly vulnerable to oxidative damage due to their high metabolic activity, lipid-rich membranes, and limited regenerative capacity. Excessive ROS can lead to mitochondrial dysfunction, impaired homeostasis, DNA damage, and the activation of pro-death signaling cascades, all contributing to the loss of neuronal integrity and function seen in disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Recent advances in neurobiology and redox research have highlighted novel therapeutic strategies aimed at reducing oxidative damage or enhancing endogenous antioxidant responses. These include small-molecule antioxidants, natural compounds, redox-active nanoparticles, gene therapies, and modulators of redox-sensitive signaling pathways.

We invite you to submit your latest research findings or a review article to this Special Issue, which should explore innovative neuroprotective strategies that target oxidative stress in both physiological and pathological contexts. Suitable topics of interest include, but are not limited to, the following: the molecular basis of redox imbalance in the nervous system; mitochondrial-targeted antioxidants; ROS-related signaling in neurodegeneration; antioxidant-based therapeutics; and translational models of redox-targeted interventions.

Dr. Tomasz Boczek
Guest Editor

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Keywords

  • oxidative stress
  • neurodegeneration
  • antioxidant therapy
  • mitochondrial dysfunction
  • redox signaling
  • reactive oxygen species (ROS)
  • neuroprotection
  • Alzheimer’s disease
  • Parkinson’s disease
  • translational neuroscience

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Published Papers (2 papers)

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Review

30 pages, 1519 KB  
Review
Chronic Stress and Astrocyte Dysfunction in Depression: Molecular Mechanisms and Gene Expression Changes
by Natalia Bochenska, Julia Tomczak and Malwina Lisek
Antioxidants 2025, 14(12), 1464; https://doi.org/10.3390/antiox14121464 - 6 Dec 2025
Viewed by 460
Abstract
Major depressive disorder (MDD) is a complex and heterogeneous psychiatric condition with high global prevalence and significant personal and societal burdens. While traditionally focused on neuronal dysfunction, emerging research highlights a critical role for astrocytes—glial cells essential for maintaining brain homeostasis in the [...] Read more.
Major depressive disorder (MDD) is a complex and heterogeneous psychiatric condition with high global prevalence and significant personal and societal burdens. While traditionally focused on neuronal dysfunction, emerging research highlights a critical role for astrocytes—glial cells essential for maintaining brain homeostasis in the pathogenesis of depression. This review explores how chronic stress, a major risk factor for MDD, disrupts astrocyte function through multiple converging mechanisms. We detail the normal physiological roles of astrocytes in synaptic regulation, neurotransmitter cycling, metabolic support, and neurovascular integrity, and examine how these functions are compromised under chronic stress. Key molecular pathways implicated include glucocorticoid receptor (GR) signaling dysregulation, neuroinflammatory responses, glutamate excitotoxicity, oxidative stress, and epigenetic alterations. Evidence from histological and transcriptomic studies in both human postmortem tissue and rodent models reveals consistent changes in astrocyte-specific genes, such as GFAP, SLC1A2, SLC1A3, BDNF, and AQP4, supporting their involvement in depressive pathology. Finally, we discuss therapeutic strategies targeting astrocyte dysfunction—including EAAT2 upregulation, neuromodulation, anti-inflammatory approaches, GR modulation, and glial-focused epigenetic therapies. Understanding astrocyte pathology in the context of chronic stress not only refines our understanding of MDD but also opens novel avenues for treatment development. Full article
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31 pages, 1498 KB  
Review
Neuron–Glia Crosstalk in the Regulation of Astrocytic Antioxidative Mechanisms Following CNS Injury
by Piotr K. Zakrzewski and Tomasz Boczek
Antioxidants 2025, 14(12), 1415; https://doi.org/10.3390/antiox14121415 - 27 Nov 2025
Viewed by 516
Abstract
Astrocytes play a key role in maintaining redox balance and supporting neuronal survival within the central nervous system (CNS). Their antioxidant machinery, primarily involving the Nrf2–ARE (nuclear factor erythroid 2-related factor 2–antioxidant response element) pathway, glutathione (GSH) metabolism, and mitochondrial function, enables the [...] Read more.
Astrocytes play a key role in maintaining redox balance and supporting neuronal survival within the central nervous system (CNS). Their antioxidant machinery, primarily involving the Nrf2–ARE (nuclear factor erythroid 2-related factor 2–antioxidant response element) pathway, glutathione (GSH) metabolism, and mitochondrial function, enables the removal of reactive oxygen and nitrogen species (ROS and RNS) and supports neuronal resistance to oxidative stress. Effective communication between neurons and astrocytes coordinates metabolic and antioxidative responses via glutamate-, nitric oxide-, and calcium-dependent signalling. Disruption of this crosstalk during traumatic injury, ischemia, or neurodegenerative disease causes redox imbalance, neuroinflammation, and excitotoxicity, which contribute to progressive neurodegeneration. Astrocytic Nrf2 activation reduces oxidative damage and inflammation, while its suppression encourages a neurotoxic glial phenotype. Current evidence emphasizes various therapeutic strategies targeting astrocytic redox mechanisms, including small-molecule Nrf2 activators, GSH precursors, mitochondria-targeted antioxidants (MTAs), and RNA- and gene-based approaches. These interventions boost the antioxidant ability of astrocytes, influence reactive cell phenotypes, and support neuronal recovery in preclinical models. Although there are still challenges in delivery and safety, restoring neuron–glia redox signalling offers a promising strategy for neuroprotective treatments aimed at reducing oxidative stress-related CNS injury and disease progression. Full article
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