Role of Antioxidants and Oxidative Stress in Neurodegenerative Diseases

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 March 2026 | Viewed by 2972

Special Issue Editor


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Guest Editor
Department of Clinical and Biological Sciences, Università degli Studi di Torino, Turin, Italy
Interests: Alzheimer’s disease

Special Issue Information

Dear Colleagues,

Neurodegenerative disorders that affect both the central nervous system (CNS) and  the peripheral nervous system (PNS), including Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), multiple sclerosis (MS), frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), retinopathies, spinal cord illnesses, and peripheral neuropathies, are among the most significant challenges to global health worldwide, with a growing number of patients and an increasing demand for therapies aimed at preventing or treating these maladies. All these pathologies share as a common feature an impairment of the cellular redox homeostasis. This alteration is mainly due to an imbalance between the levels of pro-oxidant reactive nitrogen and oxygen species (RNS and ROS) and the antioxidant defenses of the cells. The high oxygen demand and lipid-rich environment of the nervous system make it particularly vulnerable to oxidative damage. ROS and RNS accumulation deleteriously affects neurons, glia, leucocytes, vessel wall cells, myelin, and the extracellular matrix, leading to cell death, extra- and intracellular accumulation of misfolded proteins, metabolic perturbations, synaptic dysfunction, blood–brain barrier (BBB) damage, glymphatic system failure, and hyperactivation of inflammatory responses—all events that contribute to the neurodegenerative process. Based on this, the administration of antioxidant molecules has been receiving attention as a promising strategy for curing neurodegenerative diseases. This class of compounds comprises a diverse range of chemical species, both of natural and synthetic origin, able to act not only as canonical antioxidants but also as key modulators of important signaling pathways involved in the regulation of cell redox balance, as well as viability, metabolism, protein processing, and inflammation.

The purpose of this Special Issue of Antioxidants is to provide a comprehensive overview of the latest advances in our understanding of the primary role played by oxidant and antioxidant species in the pathogenesis of neurodegenerative diseases, as well as to present recent developments in the application of antioxidants for the clinical management neurodegenerative disorders. To this end, we are calling for reviews and original contributions on this important topic.

Dr. Barbara Sottero
Guest Editor

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Keywords

  • neurodegenerative diseases
  • antioxidants
  • oxidative stress
  • Parkinson’s disease
  • Alzheimer’s disease

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Published Papers (2 papers)

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Research

30 pages, 2944 KB  
Article
Synthetic Cyclic C5-Curcuminoids Increase Antioxidant Defense and Reduce Inflammation in 6-OHDA-Induced Retinoic Acid-Differentiated SH-SY5Y Cells
by Edina Pandur, Gergely Gulyás-Fekete, Győző Kulcsár and Imre Huber
Antioxidants 2025, 14(9), 1057; https://doi.org/10.3390/antiox14091057 - 28 Aug 2025
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Abstract
Parkinson’s disease (PD) is recognized as one of the most common neurodegenerative disorders globally. The primary factor contributing to this condition is the loss of dopaminergic neurons, which results in both motor and nonmotor symptoms. The etiology of neurodegeneration remains unclear. However, it [...] Read more.
Parkinson’s disease (PD) is recognized as one of the most common neurodegenerative disorders globally. The primary factor contributing to this condition is the loss of dopaminergic neurons, which results in both motor and nonmotor symptoms. The etiology of neurodegeneration remains unclear. However, it is characterized by the elevated production of reactive oxygen species, which subsequently leads to oxidative stress, lipid peroxidation, mitochondrial dysfunction, and inflammation. The investigation of the applicability of natural compounds and their derivatives to various diseases is becoming increasingly important. The possible role of curcumin from Curcuma longa L. and its derivatives in the treatment of PD has been partially investigated, but there are no data on the action of synthetic cyclic C5-curcuminoids and chalcones tested in a Parkinson’s model. Two chalcones and five synthetic cyclic C5-curcuminoids with potential antioxidant properties were investigated in an in vitro model of 6-hydroxydopamine (6-OHDA)-induced neurodegeneration in differentiated SH-SY5Y cells. Reactive oxygen species (ROS) production, total antioxidant capacity, antioxidant enzyme activity, thiol and ATP levels, caspase-3 activity, and cytokine release were examined after treatment with the test compounds. Based on these results, one cyclic chalcone (compound 5) and three synthetic cyclic C5-curcuminoids (compounds 9, 12, and 13) decreased oxidative stress and apoptosis in our in vitro model of neurodegeneration. Compounds 5 and 9 were also successful in decreasing the production of pro-inflammatory cytokines (IL-6, IL-8, and TNF-α), while promoting the release of anti-inflammatory cytokines (IL-4 and IL-10). These findings indicate that these two compounds exhibit potential antioxidant, anti-apoptotic, and anti-inflammatory properties, rendering them promising candidates for drug development. Full article
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15 pages, 932 KB  
Article
Elevated Oxidative Stress in Patients with Coexisting Multiple Sclerosis and Migraine: A Cross-Sectional Study
by Iwona Rościszewska-Żukowska, Marek Biesiadecki, Mateusz Mołoń, Aleksandra Rożek, Halina Bartosik-Psujek and Sabina Galiniak
Antioxidants 2025, 14(5), 511; https://doi.org/10.3390/antiox14050511 - 24 Apr 2025
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Abstract
One potential association that is gaining increasing attention is the link between multiple sclerosis (MS) and migraine, which are suggested to frequently coexist in young patients. This is the first study to analyze the levels of multiple markers of oxidative stress in sociodemographically [...] Read more.
One potential association that is gaining increasing attention is the link between multiple sclerosis (MS) and migraine, which are suggested to frequently coexist in young patients. This is the first study to analyze the levels of multiple markers of oxidative stress in sociodemographically similar groups of patients with migraine, MS, and both MS and migraine. A single cross-sectional study was conducted at the Department of Neurology, Rzeszów University. The study included 110 participants, comprising 26 healthy controls, 24 subjects with migraines, 30 with MS, and 30 with both MS and migraine. Oxidative stress markers were measured in patients’ serum. Patients with MS and migraines had statistically elevated levels of 3-nitrotyrosine, Amadori products, 4-hydroxy-nonenal, and oxidative damage to amino acids. Moreover, we observed reduced levels of thiol groups and total antioxidant capacity in the serum of patients with MS and migraines compared to healthy controls. The co-occurrence of migraines in MS leads to greater oxidative stress than MS alone. The impact of chronic oxidative stress on both MS and migraines may exacerbate symptoms and deteriorate the quality of life. Full article
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