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Antioxidants
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Oxidative Stress and Antioxidants in Neurodegenerative Disorders 2nd Edition
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Oxidative Stress and Antioxidants in Neurodegenerative Disorders 2nd 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: 30 September 2024 | Viewed by 9619

Special Issue Editor

Prof. Dr. Marco Tulio Núñez

E-Mail Website
Guest Editor
Faculty of Sciences, Universidad de Chile, Santiago, Chile
Interests: iron homeostasis; neurodegenerative diseases; multi-target drugs; reactive oxygen species; iron/calcium interaction in the nervous system; intestinal iron absorption
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Growing evidence has indicated that oxidative stress, mitochondria dysfunction, inflammation, lysosomal dysfunction, protein aggregation and iron deposition are key factors leading to neuronal death in neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Huntington's disease and a heterogeneous group of disorders known as neurodegeneration with brain iron accumulation. Increasingly, it has been acknowledged that several of these factors are intertwined, generating positive feed-back loops that conclude in neuronal dysfunction and death.

Reactive oxygen species are central in these positive loops, since they contribute to mitochondria dysfunction and, together with iron, to lipid peroxidation and ferroptosis.

Antioxidants, in particular lipophilic antioxidants, are of clinical interest, since they have the potential to stop the lipid peroxidation cycle iniciated by the hydroxyl radical, as well as protein aggregation and nucleic acid damage.

The understanding of how these different players, manely, oxidative stress, protein aggregation, mitochondrial dysfunction and inflammation interact to generate neurodegeneration is an open field of enormous importance. Equally relevant is the design of therapeutic strategies based in the abrogation of positive feed-back loops that leed to neuronal death. In the design of these strategies, antioxidants, iron chelators and anti-inflammatory effectors are most important participants.

Prof. Dr. Marco Tulio Núñez
Guest Editor

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

  • neurodegenerative diseases, oxidative stress
  • antioxidants
  • ferroptosis
  • mitochondria dysfuction
  • protein aggregation
  • inflammation

Published Papers (6 papers)

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Research

Jump to: Review

27 pages, 6676 KiB  
Article
Beneficial Effects of Sideritis clandestina Extracts and Sideridiol against Amyloid β Toxicity
by Anna Gioran, Yiorgos Paikopoulos, Eleni Panagiotidou, Aikaterini E. I. Rizou, Georgia I. Nasi, Virginia D. Dimaki, Konstantina D. Vraila, Dimitra S. Bezantakou, Panagiotis M. Spatharas, Nikos C. Papandreou, Vassiliki Magafa, Fotini N. Lamari, Vassiliki A. Iconomidou and Niki Chondrogianni
Antioxidants 2024, 13(3), 261; https://doi.org/10.3390/antiox13030261 - 21 Feb 2024
Cited by 1 | Viewed by 1131
Abstract
Alzheimer’s disease (AD) is the most common form of dementia. Given the link between oxidative stress and AD, many studies focus on the identification of natural antioxidants against AD. Although their antioxidant capacity is important, increasing data suggest that additional activities are related [...] Read more.
Alzheimer’s disease (AD) is the most common form of dementia. Given the link between oxidative stress and AD, many studies focus on the identification of natural antioxidants against AD. Although their antioxidant capacity is important, increasing data suggest that additional activities are related to their beneficial effects, including properties against amyloid beta (Aβ) aggregation. Sideritis spp. (mountain tea) extracts possess not only antioxidant activity but also other bioactivities that confer neuroprotection. Although various Sideritis spp. extracts have been extensively studied, there are scarce data on S. clandestina subsp. peloponnesiaca (SCP) phytochemical composition and neuroprotective potential, while nothing is known of the responsible compounds. Given that SCP is a weaker antioxidant compared to other Sideritis spp., here, we investigated its potential beneficial properties against Aβ aggregation. We characterized different SCP extracts and revealed their anti-aggregation activity by taking advantage of established C. elegans AD models. Importantly, we identified two pure compounds, namely, sideridiol and verbascoside, being responsible for the beneficial effects. Furthermore, we have revealed a potential anti-Aβ aggregation mechanism for sideridiol. Our results support the use of mountain tea in the elderly against dementia and demonstrate the activity of sideridiol against Aβ aggregation that could be exploited for drug development. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Neurodegenerative Disorders 2nd Edition)
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23 pages, 4696 KiB  
Article
Progesterone Receptor Membrane Component 1 Regulates Cellular Stress Responses and Inflammatory Pathways in Chronic Neuroinflammatory Conditions
by Seong-Lae Jo and Eui-Ju Hong
Antioxidants 2024, 13(2), 230; https://doi.org/10.3390/antiox13020230 - 13 Feb 2024
Viewed by 881
Abstract
Alzheimer’s disease (AD) is the leading cause of dementia and is one of the neurodegenerative diseases that are caused by neuronal death due to various triggers. Neuroinflammation plays a critical role in the development of AD. The neuroinflammatory response is manifested by pro-inflammatory [...] Read more.
Alzheimer’s disease (AD) is the leading cause of dementia and is one of the neurodegenerative diseases that are caused by neuronal death due to various triggers. Neuroinflammation plays a critical role in the development of AD. The neuroinflammatory response is manifested by pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α; various chemokines; nitrous oxide; and reactive oxygen species. In this study, we evaluated the relevance of progesterone receptor membrane component 1 (PGRMC1), which is expressed in the brain cells during the induction of neuroinflammation. A lipopolysaccharide (LPS)-induced chronic neuroinflammation model and Pgrmc1 knockdown cells were used to assess the inflammatory cytokine levels, AD-related factors, inflammation-related signaling, and cell death. Pgrmc1 knockout (KO) mice had higher IL-1β levels after treatment with LPS compared with those of wild-type (WT) mice. Furthermore, Pgrmc1 KO mice had higher levels of inflammatory factors, endoplasmic reticulum stress indicators, and AD-associated markers compared with those of WT mice who underwent LPS treatment or not. Finally, these indicators were observed in vitro using U373-MG astrocytes. In conclusion, the loss of PGRMC1 may promote neuroinflammation and lead to AD. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Neurodegenerative Disorders 2nd Edition)
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27 pages, 6369 KiB  
Article
Age-Dependent Changes in Nrf2/Keap1 and Target Antioxidant Protein Expression Correlate to Lipoxidative Adducts, and Are Modulated by Dietary N-3 LCPUFA in the Hippocampus of Mice
by Mario Díaz, Catalina Valdés-Baizabal, Daniel Pereda de Pablo and Raquel Marin
Antioxidants 2024, 13(2), 206; https://doi.org/10.3390/antiox13020206 - 6 Feb 2024
Cited by 1 | Viewed by 1024
Abstract
The brain has a high metabolism rate that may generate reactive oxygen and nitrogen species. Consequently, nerve cells require highly efficient antioxidant defenses in order to prevent a condition of deleterious oxidative stress. This is particularly relevant in the hippocampus, a highly complex [...] Read more.
The brain has a high metabolism rate that may generate reactive oxygen and nitrogen species. Consequently, nerve cells require highly efficient antioxidant defenses in order to prevent a condition of deleterious oxidative stress. This is particularly relevant in the hippocampus, a highly complex cerebral area involved in processing superior cognitive functions. Most current evidence points to hippocampal oxidative damage as a causal effect for neurodegenerative disorders, especially Alzheimer’s disease. Nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/Keap1) is a master key for the transcriptional regulation of antioxidant and detoxifying systems. It is ubiquitously expressed in brain areas, mainly supporting glial cells. In the present study, we have analyzed the relationships between Nrf2 and Keap1 isoforms in hippocampal tissue in response to aging and dietary long-chain polyunsaturated fatty acids (LCPUFA) supplementation. The possible involvement of lipoxidative and nitrosative by-products in the dynamics of the Nrf2/Keap1 complex was examined though determination of protein adducts, namely malondialdehyde (MDA), 4-hydroxynonenal (HNE), and 3-nitro-tyrosine (NTyr) under basal conditions. The results were correlated to the expression of target proteins heme-oxygenase-1 (HO-1) and glutathione peroxidase 4 (GPx4), whose expressions are known to be regulated by Nrf2/Keap1 signaling activation. All variables in this study were obtained simultaneously from the same preparations, allowing multivariate approaches. The results demonstrate a complex modification of the protein expression patterns together with the formation of adducts in response to aging and diet supplementation. Both parameters exhibited a strong interaction. Noticeably, LCPUFA supplementation to aged animals restored the Nrf2/Keap1/target protein patterns to the status observed in young animals, therefore driving a “rejuvenation” of hippocampal antioxidant defense. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Neurodegenerative Disorders 2nd Edition)
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18 pages, 4616 KiB  
Article
IP3R-Mediated Calcium Release Promotes Ferroptotic Death in SH-SY5Y Neuroblastoma Cells
by Joaquín Campos, Silvia Gleitze, Cecilia Hidalgo and Marco T. Núñez
Antioxidants 2024, 13(2), 196; https://doi.org/10.3390/antiox13020196 - 4 Feb 2024
Viewed by 1432
Abstract
Ferroptosis is an iron-dependent cell death pathway that involves the depletion of intracellular glutathione (GSH) levels and iron-mediated lipid peroxidation. Ferroptosis is experimentally caused by the inhibition of the cystine/glutamate antiporter xCT, which depletes cells of GSH, or by inhibition of glutathione peroxidase [...] Read more.
Ferroptosis is an iron-dependent cell death pathway that involves the depletion of intracellular glutathione (GSH) levels and iron-mediated lipid peroxidation. Ferroptosis is experimentally caused by the inhibition of the cystine/glutamate antiporter xCT, which depletes cells of GSH, or by inhibition of glutathione peroxidase 4 (GPx4), a key regulator of lipid peroxidation. The events that occur between GPx4 inhibition and the execution of ferroptotic cell death are currently a matter of active research. Previous work has shown that calcium release from the endoplasmic reticulum (ER) mediated by ryanodine receptor (RyR) channels contributes to ferroptosis-induced cell death in primary hippocampal neurons. Here, we used SH-SY5Y neuroblastoma cells, which do not express RyR channels, to test if calcium release mediated by the inositol 1,4,5-trisphosphate receptor (IP3R) channel plays a role in this process. We show that treatment with RAS Selective Lethal Compound 3 (RSL3), a GPx4 inhibitor, enhanced reactive oxygen species (ROS) generation, increased cytoplasmic and mitochondrial calcium levels, increased lipid peroxidation, and caused cell death. The RSL3-induced calcium signals were inhibited by Xestospongin B, a specific inhibitor of the ER-resident IP3R calcium channel, by decreasing IP3R levels with carbachol and by IP3R1 knockdown, which also prevented the changes in cell morphology toward roundness induced by RSL3. Intracellular calcium chelation by incubation with BAPTA-AM inhibited RSL3-induced calcium signals, which were not affected by extracellular calcium depletion. We propose that GPx4 inhibition activates IP3R-mediated calcium release in SH-SY5Y cells, leading to increased cytoplasmic and mitochondrial calcium levels, which, in turn, stimulate ROS production and induce lipid peroxidation and cell death in a noxious positive feedback cycle. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Neurodegenerative Disorders 2nd Edition)
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Review

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17 pages, 2114 KiB  
Review
Neuroprotective Properties of Berberine: Molecular Mechanisms and Clinical Implications
by Erjie Tian, Gaurav Sharma and Chongshan Dai
Antioxidants 2023, 12(10), 1883; https://doi.org/10.3390/antiox12101883 - 19 Oct 2023
Cited by 7 | Viewed by 2725
Abstract
Berberine (BBR), an isoquinoline alkaloid natural product, is isolated primarily from Coptis chinensis and other Berberis plants. BBR possesses various bioactivities, including antioxidant, anti-inflammation, anticancer, immune-regulation, and antimicrobial activities. Growing scientific evidence underscores BBR’s substantial neuroprotective potential, prompting increased interest and scrutiny. In [...] Read more.
Berberine (BBR), an isoquinoline alkaloid natural product, is isolated primarily from Coptis chinensis and other Berberis plants. BBR possesses various bioactivities, including antioxidant, anti-inflammation, anticancer, immune-regulation, and antimicrobial activities. Growing scientific evidence underscores BBR’s substantial neuroprotective potential, prompting increased interest and scrutiny. In this comprehensive review, we elucidate the neuroprotective attributes of BBR, delineate the underlying molecular mechanisms, and assess its clinical safety and efficacy. The multifaceted molecular mechanisms responsible for BBR’s neuroprotection encompass the attenuation of oxidative stress, mitigation of inflammatory responses, inhibition of apoptotic pathways, facilitation of autophagic processes, and modulation of CYP450 enzyme activities, neurotransmitter levels, and gut microbiota composition. Furthermore, BBR engages numerous signaling pathways, including the PI3K/Akt, NF-κB, AMPK, CREB, Nrf2, and MAPK pathways, to confer its neuroprotective effects. This comprehensive review aims to provide a substantial knowledge base, stimulate broader scientific discourse, and facilitate advancements in the application of BBR for neuroprotection. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Neurodegenerative Disorders 2nd Edition)
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26 pages, 1571 KiB  
Review
Optogenetics in Alzheimer’s Disease: Focus on Astrocytes
by Elena Mitroshina, Elizaveta Kalinina and Maria Vedunova
Antioxidants 2023, 12(10), 1856; https://doi.org/10.3390/antiox12101856 - 13 Oct 2023
Cited by 1 | Viewed by 1922
Abstract
Alzheimer’s disease (AD) is the most common form of dementia, resulting in disability and mortality. The global incidence of AD is consistently surging. Although numerous therapeutic agents with promising potential have been developed, none have successfully treated AD to date. Consequently, the pursuit [...] Read more.
Alzheimer’s disease (AD) is the most common form of dementia, resulting in disability and mortality. The global incidence of AD is consistently surging. Although numerous therapeutic agents with promising potential have been developed, none have successfully treated AD to date. Consequently, the pursuit of novel methodologies to address neurodegenerative processes in AD remains a paramount endeavor. A particularly promising avenue in this search is optogenetics, enabling the manipulation of neuronal activity. In recent years, research attention has pivoted from neurons to glial cells. This review aims to consider the potential of the optogenetic correction of astrocyte metabolism as a promising strategy for correcting AD-related disorders. The initial segment of the review centers on the role of astrocytes in the genesis of neurodegeneration. Astrocytes have been implicated in several pathological processes associated with AD, encompassing the clearance of β-amyloid, neuroinflammation, excitotoxicity, oxidative stress, and lipid metabolism (along with a critical role in apolipoprotein E function). The effect of astrocyte–neuronal interactions will also be scrutinized. Furthermore, the review delves into a number of studies indicating that changes in cellular calcium (Ca2+) signaling are one of the causes of neurodegeneration. The review’s latter section presents insights into the application of various optogenetic tools to manipulate astrocytic function as a means to counteract neurodegenerative changes. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Neurodegenerative Disorders 2nd Edition)
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