The Interplay of Oxidative Stress, the Gut–Brain Axis, and 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: 30 November 2024 | Viewed by 6500

Special Issue Editor


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Guest Editor
Department of Biomedical and Biotechnological Sciences, University of Catania, 95125 Catania, Italy
Interests: oxidative stress; nutritional antioxidants; hormesis; neuroprotection; inflammation; Nrf2 pathway; mitochondrial dysfunction; neuronal organoids; neurodegeneration; personalized nutritional therapy
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Special Issue Information

Dear Colleagues,

The antioxidant and anti-inflammatory effects of polyphenols for enhancing human stress resilience in health and disease have received more attention. Recently, the gut–brain axis (GBA) has gained attention for preventing and therapeutically impacting neuropathologies and gastrointestinal diseases. Polyphenols and polyphenol-combined nanoparticles in synergy with probiotics are shown to improve their gut bioavailability and blood–brain barrier (BBB) permeability, thus inhibiting oxidative stress, metabolic dysfunction, and inflammation linked to gut dysbiosis and the consequent onset and progression of nervous system disorders. According to hormesis, nutrients exhibit biphasic dose–response effects, activating low-dose antioxidant signaling pathways, as in the case of the Nrf2 pathway upregulated by hydroxytyrosol or curcumin and NAD/NADH-sirtuin-1 activated by resveratrol to block ROS production, microbiota dysfunction, and neurotoxic damage. Importantly, modulating the composition and function of gut microbiota through polyphenols increases the abundance of beneficial bacteria and can prevent and treat Alzheimer’s disease and also other neurological disorders. The Special Issue mainly focuses on oxidative stress and the role of hormetic nutrients by summarizing their neuroprotective and anti-inflammatory properties as well as pharmacological interventions in gut–brain disorders.

Dr. Maria Concetta Scuto
Guest Editor

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Keywords

  • oxidative stress
  • hormetic nutrients
  • natural antioxidants
  • neurodegenerative disorders
  • gut–brain axis

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Published Papers (3 papers)

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Review

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19 pages, 2066 KiB  
Review
The Involvement of Antioxidants in Cognitive Decline and Neurodegeneration: Mens Sana in Corpore Sano
by Claudio Nazzi, Alessio Avenanti and Simone Battaglia
Antioxidants 2024, 13(6), 701; https://doi.org/10.3390/antiox13060701 - 7 Jun 2024
Cited by 5 | Viewed by 1595
Abstract
With neurodegenerative disorders being on the rise, a great deal of research from multiple fields is being conducted in order to further knowledge and propose novel therapeutic interventions. Among these investigations, research on the role of antioxidants in contrasting cognitive decline is putting [...] Read more.
With neurodegenerative disorders being on the rise, a great deal of research from multiple fields is being conducted in order to further knowledge and propose novel therapeutic interventions. Among these investigations, research on the role of antioxidants in contrasting cognitive decline is putting forward interesting and promising results. In this review, we aim to collect evidence that focused on the role of a variety of antioxidants and antioxidant-rich foods in improving or stabilizing cognitive functions, memory, and Alzheimer’s disease, the most common neurodegenerative disorder. Specifically, we considered evidence collected on humans, either through longitudinal studies or randomized, placebo-controlled ones, which evaluated cognitive performance, memory abilities, or the progression level of neurodegeneration. Overall, despite a great deal of variety between study protocols, cohorts of participants involved, neuropsychological tests used, and investigated antioxidants, there is a solid trend that suggests that the properties of antioxidants may be helpful in hampering cognitive decline in older people. Thus, the help of future research that will further elucidate the role of antioxidants in neuroprotection will lead to the development of novel interventions that will take into account such findings to provide a more global approach to treating neurodegenerative disorders. Full article
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41 pages, 3286 KiB  
Review
Hormetic Nutrition and Redox Regulation in Gut–Brain Axis Disorders
by Maria Scuto, Francesco Rampulla, Giuseppe Maria Reali, Sestina Maria Spanò, Angela Trovato Salinaro and Vittorio Calabrese
Antioxidants 2024, 13(4), 484; https://doi.org/10.3390/antiox13040484 - 18 Apr 2024
Cited by 15 | Viewed by 3129
Abstract
The antioxidant and anti-inflammatory effects of hormetic nutrition for enhancing stress resilience and overall human health have received much attention. Recently, the gut–brain axis has attracted prominent interest for preventing and therapeutically impacting neuropathologies and gastrointestinal diseases. Polyphenols and polyphenol-combined nanoparticles in synergy [...] Read more.
The antioxidant and anti-inflammatory effects of hormetic nutrition for enhancing stress resilience and overall human health have received much attention. Recently, the gut–brain axis has attracted prominent interest for preventing and therapeutically impacting neuropathologies and gastrointestinal diseases. Polyphenols and polyphenol-combined nanoparticles in synergy with probiotics have shown to improve gut bioavailability and blood–brain barrier (BBB) permeability, thus inhibiting the oxidative stress, metabolic dysfunction and inflammation linked to gut dysbiosis and ultimately the onset and progression of central nervous system (CNS) disorders. In accordance with hormesis, polyphenols display biphasic dose–response effects by activating at a low dose the Nrf2 pathway resulting in the upregulation of antioxidant vitagenes, as in the case of heme oxygenase-1 upregulated by hidrox® or curcumin and sirtuin-1 activated by resveratrol to inhibit reactive oxygen species (ROS) overproduction, microbiota dysfunction and neurotoxic damage. Importantly, modulation of the composition and function of the gut microbiota through polyphenols and/or probiotics enhances the abundance of beneficial bacteria and can prevent and treat Alzheimer’s disease and other neurological disorders. Interestingly, dysregulation of the Nrf2 pathway in the gut and the brain can exacerbate selective susceptibility under neuroinflammatory conditions to CNS disorders due to the high vulnerability of vagal sensory neurons to oxidative stress. Herein, we aimed to discuss hormetic nutrients, including polyphenols and/or probiotics, targeting the Nrf2 pathway and vitagenes for the development of promising neuroprotective and therapeutic strategies to suppress oxidative stress, inflammation and microbiota deregulation, and consequently improve cognitive performance and brain health. In this review, we also explore interactions of the gut–brain axis based on sophisticated and cutting-edge technologies for novel anti-neuroinflammatory approaches and personalized nutritional therapies. Full article
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Other

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21 pages, 1764 KiB  
Systematic Review
Redox Homeostasis, Gut Microbiota, and Epigenetics in Neurodegenerative Diseases: A Systematic Review
by Constantin Munteanu, Anca Irina Galaction, Marius Turnea, Corneliu Dan Blendea, Mariana Rotariu and Mădălina Poștaru
Antioxidants 2024, 13(9), 1062; https://doi.org/10.3390/antiox13091062 - 30 Aug 2024
Viewed by 1287
Abstract
Neurodegenerative diseases encompass a spectrum of disorders marked by the progressive degeneration of the structure and function of the nervous system. These conditions, including Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis (MS), often lead [...] Read more.
Neurodegenerative diseases encompass a spectrum of disorders marked by the progressive degeneration of the structure and function of the nervous system. These conditions, including Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis (MS), often lead to severe cognitive and motor deficits. A critical component of neurodegenerative disease pathologies is the imbalance between pro-oxidant and antioxidant mechanisms, culminating in oxidative stress. The brain’s high oxygen consumption and lipid-rich environment make it particularly vulnerable to oxidative damage. Pro-oxidants such as reactive nitrogen species (RNS) and reactive oxygen species (ROS) are continuously generated during normal metabolism, counteracted by enzymatic and non-enzymatic antioxidant defenses. In neurodegenerative diseases, this balance is disrupted, leading to neuronal damage. This systematic review explores the roles of oxidative stress, gut microbiota, and epigenetic modifications in neurodegenerative diseases, aiming to elucidate the interplay between these factors and identify potential therapeutic strategies. We conducted a comprehensive search of articles published in 2024 across major databases, focusing on studies examining the relationships between redox homeostasis, gut microbiota, and epigenetic changes in neurodegeneration. A total of 161 studies were included, comprising clinical trials, observational studies, and experimental research. Our findings reveal that oxidative stress plays a central role in the pathogenesis of neurodegenerative diseases, with gut microbiota composition and epigenetic modifications significantly influencing redox balance. Specific bacterial taxa and epigenetic markers were identified as potential modulators of oxidative stress, suggesting novel avenues for therapeutic intervention. Moreover, recent evidence from human and animal studies supports the emerging concept of targeting redox homeostasis through microbiota and epigenetic therapies. Future research should focus on validating these targets in clinical settings and exploring the potential for personalized medicine strategies based on individual microbiota and epigenetic profiles. Full article
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