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Connecting the Dots between Oxidative Stress, Gut-Brain Axis and Neurodegenerative Diseases

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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: closed (30 November 2022) | Viewed by 32063

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Special Issue Editors

Dr. Ana Raquel F. Esteves

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Center for Neuroscience & Cell Biology, Faculty of Medicine, 1st floor, University of Coimbra, Coimbra, Portugal
Interests: Disclose the molecular mechanism and potential therapeutic targets that can cure or delay the progression of neurodegenerative disorders, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). My research interests involve a strong component in translational research with the main focus in studying mitochondrial signalling, axonal dynamics and trafficking, endopasmatic reticulum function and calcium homeostasis; intracellular proteolytic systems such as autophagy-lysosomal system and the ubiquitin–proteasome pathway and inflammatory responses in neurodegeneration.

Dr. Diana Silva

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Center for Neuroscience & Cell Biology, Faculty of Medicine, 1st floor, University of Coimbra, Coimbra, Portugal
Interests: Investigate the molecular mechanisms of neurodegeneration involved in Alzheimer`s disease (AD) and Parkinson´s disease, particularly the signaling role of mitochondria in neuronal death. Evaluate the role of mitochondrial dysfunction on mediating microtubule depolymerization, protein aggregation, and innate immune responses activation and its relevance to the progression of neurodegenerative diseases.

Special Issue Information

Dear Colleagues,

Oxidative stress has been remarkably implicated in the progression of several neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). Moreover, neuroinflammation is consistently reported to be deregulated in these diseases and to facilitate disease progression. Recent findings suggest the crucial role of mitochondrial proteins and mitochondrial reactive oxygen species, recognized as damage-associated molecular patterns (DAMPs), in the intracellular signaling that regulates innate immunity and inflammation. Indeed, inflammation is deeply entangled with redox modulation, however, the link between these two is poorly understood. Moreover, the gut-brain axis consists in the bidirectional interaction between intestinal microbiota, the gut, and the Central Nervous System (CNS), with the exchange of hormones, neurotransmitters, and neurotoxic metabolites. Emerging evidence highlights that during normal aging, the microbiota that populates Enteric Nervous System (ENS) suffers changes which result in altered permeability of the intestinal barrier and that these mechanisms may be involved in several neurodegenerative disorders. Interestingly, some reports suggest that certain bacteria taxa increase brain inflammation and reactive oxygen species levels, which might favor abnormal aggregation of proteins, a known neuropathological hallmark of diseases like PD and AD.

Therefore we invite investigators to submit original research or review articles with their latest valuable research outcomes for publication in the Special Issue entitled "Connecting the dots between oxidative stress, gut-brain axis, and neurodegenerative disorders" for the Antioxidants journal (MDPI). Topics in this Special Issue include, but are not limited to, the following:

Role of gut microbiota in combating or generating oxidative stress.
Oxidative stress and inflammation in the pathogenesis of neurodegenerative diseases.
Potential interactions between the microbiota-gut-brain axis and the CNS’s oxidative stress.
Oxidative stress, microbiome, and gut health
Antioxidants and the gut microbiome

We look forward to your contribution.

Dr. Ana Raquel F. Esteves
Dr. Diana Silva
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Oxidative stress
Mitochondrial dysfunction
Neuroinflammation
Gut microbiota
Neurodegenerative diseases
Gut-brain axis

Published Papers (7 papers)

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Research

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14 pages, 1795 KiB

Open AccessArticle

Agaricus Mushroom-Enriched Diets Modulate the Microbiota-Gut-Brain Axis and Reduce Brain Oxidative Stress in Mice

by Josune García-Sanmartín, Miriam Bobadilla, Eduardo Mirpuri, Vanessa Grifoll, Margarita Pérez-Clavijo and Alfredo Martínez

Antioxidants 2022, 11(4), 695; https://doi.org/10.3390/antiox11040695 - 31 Mar 2022

Cited by 6 | Viewed by 3429

Abstract

Neurodegenerative diseases pose a major problem for developed countries, and stress has been identified as one of the main risk factors in the development of these disorders. Here, we have examined the protective properties against brain oxidative stress of two diets supplemented with 5% (w/w) of Agaricus bisporus (white button mushroom) or Agaricus bisporus brunnescens (Portobello mushroom) in mice. These diets did not modify the weight gain of the animals when compared to those fed with a regular diet, even after feeding on them for 15 weeks. The long-term modification of the microbiota after 12 weeks on the diets was investigated. At the phylum level, there was a large increase of Verrucomicrobia and a reduction of Cyanobacteria associated with the mushroom diets. No changes were observed in the Firmicutes/Bacteroidetes ratio, whose stability is a marker for a healthy diet. At the family level, three groups presented significant variations. These included Akkermansiaceae and Tannerellaceae, which significantly increased with both diets; and Prevotellaceae, which significantly decreased with both diets. These bacteria participate in the generation of microbiota-derived short-chain fatty acids (SCFAs) and provide a link between the microbiota and the brain. Mice subjected to restraint stress showed an upregulation of Il-6, Nox-2, and Hmox-1 expression; a reduction in the enzymatic activities of catalase and superoxide dismutase; and an increase in lipid peroxidation in their brains. All these parameters were significantly prevented by feeding for 3 weeks on the Agaricus-supplemented diets. In summary, the supplementation of a healthy diet with Agaricus mushrooms may significantly contribute to prevent neurodegenerative diseases in the general population. Full article

(This article belongs to the Special Issue Connecting the Dots between Oxidative Stress, Gut-Brain Axis and Neurodegenerative Diseases)

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21 pages, 2724 KiB

Open AccessArticle

Failure of the Brain Glucagon-Like Peptide-1-Mediated Control of Intestinal Redox Homeostasis in a Rat Model of Sporadic Alzheimer’s Disease

by Jan Homolak, Ana Babic Perhoc, Ana Knezovic, Jelena Osmanovic Barilar and Melita Salkovic-Petrisic

Antioxidants 2021, 10(7), 1118; https://doi.org/10.3390/antiox10071118 - 13 Jul 2021

Cited by 14 | Viewed by 3019

Abstract

The gastrointestinal system may be involved in the etiopathogenesis of the insulin-resistant brain state (IRBS) and Alzheimer’s disease (AD). Gastrointestinal hormone glucagon-like peptide-1 (GLP-1) is being explored as a potential therapy as activation of brain GLP-1 receptors (GLP-1R) exerts neuroprotection and controls peripheral metabolism. Intracerebroventricular administration of streptozotocin (STZ-icv) is used to model IRBS and GLP-1 dyshomeostasis seems to be involved in the development of neuropathological changes. The aim was to explore (i) gastrointestinal homeostasis in the STZ-icv model (ii) assess whether the brain GLP-1 is involved in the regulation of gastrointestinal redox homeostasis and (iii) analyze whether brain-gut GLP-1 axis is functional in the STZ-icv animals. Acute intracerebroventricular treatment with exendin-3(9-39)amide was used for pharmacological inhibition of brain GLP-1R in the control and STZ-icv rats, and oxidative stress was assessed in plasma, duodenum and ileum. Acute inhibition of brain GLP-1R increased plasma oxidative stress. TBARS were increased, and low molecular weight thiols (LMWT), protein sulfhydryls (SH), and superoxide dismutase (SOD) were decreased in the duodenum, but not in the ileum of the controls. In the STZ-icv, TBARS and CAT were increased, LMWT and SH were decreased at baseline, and no further increment of oxidative stress was observed upon central GLP-1R inhibition. The presented results indicate that (i) oxidative stress is increased in the duodenum of the STZ-icv rat model of AD, (ii) brain GLP-1R signaling is involved in systemic redox regulation, (iii) brain-gut GLP-1 axis regulates duodenal, but not ileal redox homeostasis, and iv) brain-gut GLP-1 axis is dysfunctional in the STZ-icv model. Full article

(This article belongs to the Special Issue Connecting the Dots between Oxidative Stress, Gut-Brain Axis and Neurodegenerative Diseases)

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Review

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25 pages, 1188 KiB

Open AccessReview

Neurodegenerative Microbially-Shaped Diseases: Oxidative Stress Meets Neuroinflammation

by Diana Filipa Silva, Nuno Empadinhas, Sandra Morais Cardoso and Ana Raquel Esteves

Antioxidants 2022, 11(11), 2141; https://doi.org/10.3390/antiox11112141 - 28 Oct 2022

Cited by 7 | Viewed by 2798

Abstract

Inflammation and oxidative stress characterize a number of chronic conditions including neurodegenerative diseases and aging. Inflammation is a key component of the innate immune response in Alzheimer’s disease and Parkinson’s disease of which oxidative stress is an important hallmark. Immune dysregulation and mitochondrial dysfunction with concomitant reactive oxygen species accumulation have also been implicated in both diseases, both systemically and within the Central Nervous System. Mitochondria are a centrally positioned signalling hub for inflammatory responses and inflammatory cells can release reactive species at the site of inflammation often leading to exaggerated oxidative stress. A growing body of evidence suggests that disruption of normal gut microbiota composition may induce increased permeability of the gut barrier leading to chronic systemic inflammation, which may, in turn, impair the blood–brain barrier function and promote neuroinflammation and neurodegeneration. The gastrointestinal tract is constantly exposed to myriad exogenous substances and microbial pathogens, which are abundant sources of reactive oxygen species, oxidative damage and pro-inflammatory events. Several studies have demonstrated that microbial infections may also affect the balance in gut microbiota composition (involving oxidant and inflammatory processes by the host and indigenous microbiota) and influence downstream Alzheimer’s disease and Parkinson’s disease pathogenesis, in which blood–brain barrier damage ultimately occurs. Therefore, the oxidant/inflammatory insults triggered by a disrupted gut microbiota and chronic dysbiosis often lead to compromised gut barrier function, allowing inflammation to “escape” as well as uncontrolled immune responses that may ultimately disrupt mitochondrial function upwards the brain. Future therapeutic strategies should be designed to “restrain” gut inflammation, a goal that could ideally be attained by microbiota modulation strategies, in alternative to classic anti-inflammatory agents with unpredictable effects on the microbiota architecture itself. Full article

(This article belongs to the Special Issue Connecting the Dots between Oxidative Stress, Gut-Brain Axis and Neurodegenerative Diseases)

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22 pages, 2742 KiB

Open AccessReview

Nutraceuticals and Physical Activity as Antidepressants: The Central Role of the Gut Microbiota

by Sabrina Donati Zeppa, Fabio Ferrini, Deborah Agostini, Stefano Amatori, Elena Barbieri, Giovanni Piccoli, Piero Sestili and Vilberto Stocchi

Antioxidants 2022, 11(2), 236; https://doi.org/10.3390/antiox11020236 - 26 Jan 2022

Cited by 6 | Viewed by 4761

Abstract

Major depressive disorder (MDD) is a common mental illness. Evidence suggests that the gut microbiota play an essential role in regulating brain functions and the pathogenesis of neuropsychiatric diseases, including MDD. There are numerous mechanisms through which the gut microbiota and brain can exchange information in a continuous, bidirectional communication. Current research emphasizes the interexchange of signals influenced by the gut microbiota that are detected and transduced in information from the gut to the nervous system involving neural, endocrine, and inflammatory mechanisms, suggesting a relationship between oxidative stress and the pathophysiology of MDD via the hyperactivation of inflammatory responses. Potential sources of inflammation in the plasma and hippocampus of depressed individuals could stem from increases in intestinal permeability. Some nutraceuticals, such as specific probiotics, namely psychobiotics, polyphenols, carotenoids, butyrate, and prebiotics, have been demonstrated to exert an antidepressant activity, but most of them need to be metabolized and activated by gut microorganisms. By inducing changes in the gut microbiota composition, physical exercise might also exert a role in alleviating depression-like symptoms. The mutual relationships among nutraceuticals, exercise, and depression will be discussed, and the potential role of the gut microbiota as a therapeutic target to treat depression will be explored. Full article

(This article belongs to the Special Issue Connecting the Dots between Oxidative Stress, Gut-Brain Axis and Neurodegenerative Diseases)

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46 pages, 5115 KiB

Open AccessReview

Parkinson’s Disease and the Metal–Microbiome–Gut–Brain Axis: A Systems Toxicology Approach

by Lady Johanna Forero-Rodríguez, Jonathan Josephs-Spaulding, Stefano Flor, Andrés Pinzón and Christoph Kaleta

Antioxidants 2022, 11(1), 71; https://doi.org/10.3390/antiox11010071 - 28 Dec 2021

Cited by 10 | Viewed by 4797

Abstract

Parkinson’s Disease (PD) is a neurodegenerative disease, leading to motor and non-motor complications. Autonomic alterations, including gastrointestinal symptoms, precede motor defects and act as early warning signs. Chronic exposure to dietary, environmental heavy metals impacts the gastrointestinal system and host-associated microbiome, eventually affecting the central nervous system. The correlation between dysbiosis and PD suggests a functional and bidirectional communication between the gut and the brain. The bioaccumulation of metals promotes stress mechanisms by increasing reactive oxygen species, likely altering the bidirectional gut–brain link. To better understand the differing molecular mechanisms underlying PD, integrative modeling approaches are necessary to connect multifactorial perturbations in this heterogeneous disorder. By exploring the effects of gut microbiota modulation on dietary heavy metal exposure in relation to PD onset, the modification of the host-associated microbiome to mitigate neurological stress may be a future treatment option against neurodegeneration through bioremediation. The progressive movement towards a systems toxicology framework for precision medicine can uncover molecular mechanisms underlying PD onset such as metal regulation and microbial community interactions by developing predictive models to better understand PD etiology to identify options for novel treatments and beyond. Several methodologies recently addressed the complexity of this interaction from different perspectives; however, to date, a comprehensive review of these approaches is still lacking. Therefore, our main aim through this manuscript is to fill this gap in the scientific literature by reviewing recently published papers to address the surrounding questions regarding the underlying molecular mechanisms between metals, microbiota, and the gut–brain-axis, as well as the regulation of this system to prevent neurodegeneration. Full article

(This article belongs to the Special Issue Connecting the Dots between Oxidative Stress, Gut-Brain Axis and Neurodegenerative Diseases)

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31 pages, 3162 KiB

Open AccessReview

The Emerging Scenario of the Gut–Brain Axis: The Therapeutic Actions of the New Actor Kefir against Neurodegenerative Diseases

by Thiago M. C. Pereira, Larissa Z. Côco, Alyne M. M. Ton, Silvana S. Meyrelles, Manuel Campos-Toimil, Bianca P. Campagnaro and Elisardo C. Vasquez

Antioxidants 2021, 10(11), 1845; https://doi.org/10.3390/antiox10111845 - 20 Nov 2021

Cited by 16 | Viewed by 6551

Abstract

The fact that millions of people worldwide suffer from Alzheimer’s disease (AD) or Parkinson’s disease (PD), the two most prevalent neurodegenerative diseases (NDs), has been a permanent challenge to science. New tools were developed over the past two decades and were immediately incorporated into routines in many laboratories, but the most valuable scientific contribution was the “waking up” of the gut microbiota. Disturbances in the gut microbiota, such as an imbalance in the beneficial/pathogenic effects and a decrease in diversity, can result in the passage of undesired chemicals and cells to the systemic circulation. Recently, the potential effect of probiotics on restoring/preserving the microbiota was also evaluated regarding important metabolite and vitamin production, pathogen exclusion, immune system maturation, and intestinal mucosal barrier integrity. Therefore, the focus of the present review is to discuss the available data and conclude what has been accomplished over the past two decades. This perspective fosters program development of the next steps that are necessary to obtain confirmation through clinical trials on the magnitude of the effects of kefir in large samples. Full article

(This article belongs to the Special Issue Connecting the Dots between Oxidative Stress, Gut-Brain Axis and Neurodegenerative Diseases)

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18 pages, 1285 KiB

Open AccessReview

The Potential Role of Polyphenols in Oxidative Stress and Inflammation Induced by Gut Microbiota in Alzheimer’s Disease

by Umair Shabbir, Akanksha Tyagi, Fazle Elahi, Simon Okomo Aloo and Deog-Hwan Oh

Antioxidants 2021, 10(9), 1370; https://doi.org/10.3390/antiox10091370 - 27 Aug 2021

Cited by 26 | Viewed by 4956

Abstract

Gut microbiota (GM) play a role in the metabolic health, gut eubiosis, nutrition, and physiology of humans. They are also involved in the regulation of inflammation, oxidative stress, immune responses, central and peripheral neurotransmission. Aging and unhealthy dietary patterns, along with oxidative and inflammatory responses due to gut dysbiosis, can lead to the pathogenesis of neurodegenerative diseases, especially Alzheimer’s disease (AD). Although the exact mechanism between AD and GM dysbiosis is still unknown, recent studies claim that secretions from the gut can enhance hallmarks of AD by disturbing the intestinal permeability and blood–brain barrier via the microbiota–gut–brain axis. Dietary polyphenols are the secondary metabolites of plants that possess anti-oxidative and anti-inflammatory properties and can ameliorate gut dysbiosis by enhancing the abundance of beneficial bacteria. Thus, modulation of gut by polyphenols can prevent and treat AD and other neurodegenerative diseases. This review summarizes the role of oxidative stress, inflammation, and GM in AD. Further, it provides an overview on the ability of polyphenols to modulate gut dysbiosis, oxidative stress, and inflammation against AD. Full article

(This article belongs to the Special Issue Connecting the Dots between Oxidative Stress, Gut-Brain Axis and Neurodegenerative Diseases)

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