Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.8
7.0
Journals
Antioxidants
Special Issues
Oxidative Stress in Neurodegeneration and Neuroinflammation
share announcement

Oxidative Stress in Neurodegeneration and Neuroinflammation

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 (31 October 2021) | Viewed by 51196

Special Issue Editors

Dr. C. Henrique Alves

E-Mail Website
Guest Editor
1. Retinal Dysfunction and Neuroinflammation Lab, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
2. Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-531 Coimbra, Portugal
3. Association for Innovation and Biomedical Research on Light and Image (AIBILI), 3000-548 Coimbra, Portugal
4. Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal
Interests: microglia; retina; RPE; neurodegeneration; inflammation; CRB1; gene therapy; retinal organoids; neurodevelopment; IL-23; IL-17; mitochondria
Dr. Peter M.J. Quinn

E-Mail Website
Guest Editor
Department of Ophthalmology, Edward S. Harkness Eye Institute, Columbia University Irving Medical Center, New York, NY 10032, USA
Interests: organoids; organ chips; induced pluripotent stem cells; neurodegeneration; neuroinflammation; retina, RPE, mitochondria; microglia; Crumbs homologue-1; CRB1; metabolome reprogramming, gene augmentation; gene editing; cell therapy
Special Issues, Collections and Topics in MDPI journals
Dr. António Francisco Ambrósio

E-Mail Website
Guest Editor
1. Retinal Dysfunction and Neuroinflammation Lab, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
2. Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-531 Coimbra, Portugal
3. Association for Innovation and Biomedical Research on Light and Image (AIBILI), 3000-548 Coimbra, Portugal
4. Clinical Academic Center of Coimbra (CACC), 3004-561 Coimbra, Portugal
Interests: retina; retinal degenerative diseases (diabetic retinopathy, glaucoma, age-related macular degeneration); brain; neurodegenerative diseases; neurodevelopmental disorders; neuroinflammation; oxidative stress; microglia; glial cells; retinal pigment epithelium; neurodegeneration; neuroprotection; blood-retinal barrier; blood-brain barrier; cell-cell crosstalk

Special Issue Information

Dear Colleagues,

Oxidative stress, neurodegeneration and neuroinflammation are interrelated factors in the aetiology of several brain and retinal degenerative disorders, such as Alzheimer’s and Parkinson´s disease, retinitis pigmentosa, age-related macular degeneration and glaucoma. Oxidative stress results from the imbalance between the production and consumption of reactive oxygen species (ROS). This shift in redox homeostasis can initiate the synthesis and release of pro-inflammatory mediators and the infiltration of immune cells that can further potentiate oxidative stress. These cyclical processes, when uncontrolled, contribute to neuronal cell loss and severe tissue damage.

We invite you to submit your latest research findings or a review article to this Special Issue, “Oxidative Stress in Neurodegeneration and Neuroinflammation”. We aim to gather the latest research about the role of oxidative stress in neurodegeneration and neuroinflammation. We welcome submissions concerning all research models (e.g., in vitro, iPSC-derived cells, organoids, animal models), focusing on all the different nervous system tissues and cell types (e.g., retina, brain, spinal cord, neurons, microglia, astrocytes) and using all types of molecular and cellular approaches that contribute to unraveling and clarifying the pathophysiology and the molecular mechanisms related to neurodegenerative disorders.

We look forward to your contribution.

Dr. C. Henrique Alves
Dr. Peter M.J. Quinn
Dr. António Francisco Ambrósio

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
  • antioxidants
  • neuroinflammation
  • neurodegeneration
  • retina
  • brain
  • immune system
  • microglia
  • neurodegenerative disorders (e.g., retinitis pigmentosa, age-related macular degeneration, glaucoma, Alzheimer´s disease, Parkinson´s disease, amyotrophic lateral sclerosis)

Published Papers (15 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Editorial

Jump to: Research, Review

3 pages, 217 KiB  
Editorial
Oxidative Stress, Neuroinflammation and Neurodegeneration: The Chicken, the Egg and the Dinosaur
by Peter M. J. Quinn, António Francisco Ambrósio and Celso Henrique Alves
Antioxidants 2022, 11(8), 1554; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11081554 - 11 Aug 2022
Cited by 2 | Viewed by 1389
Abstract
Neurodegenerative diseases are characterized by the progressive degeneration of the neuronal cells and their networks, hampering the function of the central or peripheral nervous system [...] Full article
(This article belongs to the Special Issue Oxidative Stress in Neurodegeneration and Neuroinflammation)

Research

Jump to: Editorial, Review

19 pages, 4374 KiB  
Article
Reverse and Forward Electron Flow-Induced H2O2 Formation Is Decreased in α-Ketoglutarate Dehydrogenase (α-KGDH) Subunit (E2 or E3) Heterozygote Knock Out Animals
by Gergő Horváth, Gergely Sváb, Tímea Komlódi, Dora Ravasz, Gergely Kacsó, Judit Doczi, Christos Chinopoulos, Attila Ambrus and László Tretter
Antioxidants 2022, 11(8), 1487; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11081487 - 29 Jul 2022
Cited by 6 | Viewed by 2049
Abstract
α-ketoglutarate dehydrogenase complex (KGDHc), or 2-oxoglutarate dehydrogenase complex (OGDHc) is a rate-limiting enzyme in the tricarboxylic acid cycle, that has been identified in neurodegenerative diseases such as in Alzheimer’s disease. The aim of the present study was to establish the role of the [...] Read more.
α-ketoglutarate dehydrogenase complex (KGDHc), or 2-oxoglutarate dehydrogenase complex (OGDHc) is a rate-limiting enzyme in the tricarboxylic acid cycle, that has been identified in neurodegenerative diseases such as in Alzheimer’s disease. The aim of the present study was to establish the role of the KGDHc and its subunits in the bioenergetics and reactive oxygen species (ROS) homeostasis of brain mitochondria. To study the bioenergetic profile of KGDHc, genetically modified mouse strains were used having a heterozygous knock out (KO) either in the dihydrolipoyl succinyltransferase (DLST+/−) or in the dihydrolipoyl dehydrogenase (DLD+/−) subunit. Mitochondrial oxygen consumption, hydrogen peroxide (H2O2) production, and expression of antioxidant enzymes were measured in isolated mouse brain mitochondria. Here, we demonstrate that the ADP-stimulated respiration of mitochondria was partially arrested in the transgenic animals when utilizing α-ketoglutarate (α-KG or 2-OG) as a fuel substrate. Succinate and α-glycerophosphate (α-GP), however, did not show this effect. The H2O2 production in mitochondria energized with α-KG was decreased after inhibiting the adenine nucleotide translocase and Complex I (CI) in the transgenic strains compared to the controls. Similarly, the reverse electron transfer (RET)-evoked H2O2 formation supported by succinate or α-GP were inhibited in mitochondria isolated from the transgenic animals. The decrease of RET-evoked ROS production by DLST+/− or DLD+/− KO-s puts the emphasis of the KGDHc in the pathomechanism of ischemia-reperfusion evoked oxidative stress. Supporting this notion, expression of the antioxidant enzyme glutathione peroxidase was also decreased in the KGDHc transgenic animals suggesting the attenuation of ROS-producing characteristics of KGDHc. These findings confirm the contribution of the KGDHc to the mitochondrial ROS production and in the pathomechanism of ischemia-reperfusion injury. Full article
(This article belongs to the Special Issue Oxidative Stress in Neurodegeneration and Neuroinflammation)
►▼ Show Figures

Figure 1

20 pages, 14335 KiB  
Article
Vitamin B12 Reduces TDP-43 Toxicity by Alleviating Oxidative Stress and Mitochondrial Dysfunction
by Yu-Mi Jeon, Younghwi Kwon, Shinrye Lee, Seyeon Kim, Myungjin Jo, Seongsoo Lee, Sang Ryong Kim, Kiyoung Kim and Hyung-Jun Kim
Antioxidants 2022, 11(1), 82; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11010082 - 29 Dec 2021
Cited by 11 | Viewed by 3570
Abstract
TAR DNA-binding protein 43 (TDP-43) is a member of an evolutionarily conserved family of heterogeneous nuclear ribonucleoproteins that modulate multiple steps in RNA metabolic processes. Cytoplasmic aggregation of TDP-43 in affected neurons is a pathological hallmark of many neurodegenerative diseases, including amyotrophic lateral [...] Read more.
TAR DNA-binding protein 43 (TDP-43) is a member of an evolutionarily conserved family of heterogeneous nuclear ribonucleoproteins that modulate multiple steps in RNA metabolic processes. Cytoplasmic aggregation of TDP-43 in affected neurons is a pathological hallmark of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer’s disease (AD), and limbic predominant age-related TDP-43 encephalopathy (LATE). Mislocalized and accumulated TDP-43 in the cytoplasm induces mitochondrial dysfunction and reactive oxidative species (ROS) production. Here, we show that TDP-43- and rotenone-induced neurotoxicity in the human neuronal cell line SH-SY5Y were attenuated by hydroxocobalamin (Hb, vitamin B12 analog) treatment. Although Hb did not affect the cytoplasmic accumulation of TDP-43, Hb attenuated TDP-43-induced toxicity by reducing oxidative stress and mitochondrial dysfunction. Moreover, a shortened lifespan and motility defects in TDP-43-expressing Drosophila were significantly mitigated by dietary treatment with hydroxocobalamin. Taken together, these findings suggest that oral intake of hydroxocobalamin may be a potential therapeutic intervention for TDP-43-associated proteinopathies. Full article
(This article belongs to the Special Issue Oxidative Stress in Neurodegeneration and Neuroinflammation)
►▼ Show Figures

Figure 1

15 pages, 1707 KiB  
Article
An Intercellular Flow of Glutathione Regulated by Interleukin 6 Links Astrocytes and the Liver in the Pathophysiology of Amyotrophic Lateral Sclerosis
by Rafael López-Blanch, Rosario Salvador-Palmer, José M. Estrela and Elena Obrador
Antioxidants 2021, 10(12), 2007; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10122007 - 16 Dec 2021
Cited by 8 | Viewed by 2153
Abstract
Oxidative stress has been proposed as a major mechanism of damage to motor neurons associated with the progression of amyotrophic lateral sclerosis (ALS). Astrocytes are the most numerous glial cells in the central nervous system and, under physiological conditions, protect neurons from oxidative [...] Read more.
Oxidative stress has been proposed as a major mechanism of damage to motor neurons associated with the progression of amyotrophic lateral sclerosis (ALS). Astrocytes are the most numerous glial cells in the central nervous system and, under physiological conditions, protect neurons from oxidative damage. However, it is uncertain how their reactive phenotype may affect motor neurons during ALS progression. In two different ALS mouse models (SOD1G93A and FUS-R521C), we found that increased levels of proinflammatory interleukin 6 facilitate glutathione (GSH) release from the liver to blood circulation, which can reach the astrocytes and be channeled towards motor neurons as a mechanism of antioxidant protection. Nevertheless, although ALS progression is associated with an increase in GSH efflux from astrocytes, generation of reactive oxygen species also increases, suggesting that as the disease progresses, astrocyte-derived oxidative stress could be key to motor-neuron damage. Full article
(This article belongs to the Special Issue Oxidative Stress in Neurodegeneration and Neuroinflammation)
►▼ Show Figures

Figure 1

18 pages, 2812 KiB  
Article
mTOR Inhibition via Rapamycin Treatment Partially Reverts the Deficit in Energy Metabolism Caused by FH Loss in RPE Cells
by David A. Merle, Francesca Provenzano, Mohamed Ali Jarboui, Ellen Kilger, Simon J. Clark, Michela Deleidi, Angela Armento and Marius Ueffing
Antioxidants 2021, 10(12), 1944; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10121944 - 03 Dec 2021
Cited by 10 | Viewed by 3925
Abstract
Age-related macular degeneration (AMD) is a complex degenerative disease of the retina with multiple risk-modifying factors, including aging, genetics, and lifestyle choices. The combination of these factors leads to oxidative stress, inflammation, and metabolic failure in the retinal pigment epithelium (RPE) with subsequent [...] Read more.
Age-related macular degeneration (AMD) is a complex degenerative disease of the retina with multiple risk-modifying factors, including aging, genetics, and lifestyle choices. The combination of these factors leads to oxidative stress, inflammation, and metabolic failure in the retinal pigment epithelium (RPE) with subsequent degeneration of photoreceptors in the retina. The alternative complement pathway is tightly linked to AMD. In particular, the genetic variant in the complement factor H gene (CFH), which leads to the Y402H polymorphism in the factor H protein (FH), confers the second highest risk for the development and progression of AMD. Although the association between the FH Y402H variant and increased complement system activation is known, recent studies have uncovered novel FH functions not tied to this activity and highlighted functional relevance for intracellular FH. In our previous studies, we show that loss of CFH expression in RPE cells causes profound disturbances in cellular metabolism, increases the vulnerability towards oxidative stress, and modulates the activation of pro-inflammatory signaling pathways, most importantly the NF-kB pathway. Here, we silenced CFH in hTERT-RPE1 cells to investigate the mechanism by which intracellular FH regulates RPE cell homeostasis. We found that silencing of CFH results in hyperactivation of mTOR signaling along with decreased mitochondrial respiration and that mTOR inhibition via rapamycin can partially rescue these metabolic defects. To obtain mechanistic insight into the function of intracellular FH in hTERT-RPE1 cells, we analyzed the interactome of FH via immunoprecipitation followed by mass spectrometry-based analysis. We found that FH interacts with essential components of the ubiquitin-proteasomal pathway (UPS) as well as with factors associated with RB1/E2F signalling in a complement-pathway independent manner. Moreover, we found that FH silencing affects mRNA levels of the E3 Ubiquitin-Protein Ligase Parkin and PTEN induced putative kinase (Pink1), both of which are associated with UPS. As inhibition of mTORC1 was previously shown to result in increased overall protein degradation via UPS and as FH mRNA and protein levels were shown to be affected by inhibition of UPS, our data stress a potential regulatory link between endogenous FH activity and the UPS. Full article
(This article belongs to the Special Issue Oxidative Stress in Neurodegeneration and Neuroinflammation)
►▼ Show Figures

Figure 1

16 pages, 2734 KiB  
Article
Intravitreal Injection of Long-Acting Pegylated Granulocyte Colony-Stimulating Factor Provides Neuroprotective Effects via Antioxidant Response in a Rat Model of Traumatic Optic Neuropathy
by Chin-Te Huang, Yao-Tseng Wen, Tushar Dnyaneshwar Desai and Rong-Kung Tsai
Antioxidants 2021, 10(12), 1934; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10121934 - 01 Dec 2021
Cited by 5 | Viewed by 2901
Abstract
Traumatic optic neuropathy (TON) may cause severe visual loss following direct or indirect head trauma which may result in optic nerve injuries and therefore contribute to the subsequent loss of retinal ganglion cells by inflammatory mediators and reactive oxygen species (ROS). Granulocyte colony-stimulating [...] Read more.
Traumatic optic neuropathy (TON) may cause severe visual loss following direct or indirect head trauma which may result in optic nerve injuries and therefore contribute to the subsequent loss of retinal ganglion cells by inflammatory mediators and reactive oxygen species (ROS). Granulocyte colony-stimulating factor (G-CSF) provides the anti-inflammatory and anti-oxidative actions but has a short half-life and also induces leukocytosis upon typical systemic administration. The purpose of the present study was to investigate the relationship between the anti-oxidative response and neuroprotective effects of long-acting pegylated human G-CSF (PEG-G-CSF) in a rat model of optic nerve crush (ONC). Adult male Wistar rats (150–180 g) were chosen to have a sham operation in one eye and have ONC in the other. PEG-G-CSF or phosphate-buffered saline (PBS control) was immediately administered after ONC by intravitreal injection (IVI). We found the IVI of PEG-G-CSF does not induce systemic leukocytosis, but increases survival of RGCs and preserves the visual function after ONC. TUNEL assays showed fewer apoptotic cells in the retina in the PEG-G-CSF-treated eyes. The number of sorely ED1-positive cells was attenuated at the lesion site in the PEG-G-CSF-treated eyes. Immunoblotting showed up-regulation of p-Akt1, Nrf2, Sirt3, and HO-1 in the ON of the PEG-G-CSF-treated eyes. Our results demonstrated that one IVI of long-acting PEG-G-CSF is neuroprotective in the rONC. PEG-G-CSF activates the p-Akt1/Nrf2/Sirt3 and the p-Akt1/Nrf2/HO-1 axes to provide the antioxidative action and further attenuated RGC apoptosis and neuroinflammation. This provides crucial preclinical information for the development of alternative therapy with IVI of PEG-G-CSF in TON. Full article
(This article belongs to the Special Issue Oxidative Stress in Neurodegeneration and Neuroinflammation)
►▼ Show Figures

Figure 1

18 pages, 2175 KiB  
Article
Reintroduction of DJ-1 in Müller Cells Inhibits Retinal Degeneration in the DJ-1 Deficient Retina
by Naouel Gharbi, Dagne Røise, Jorunn-Elise Førre, Amanda J. Edson, Helena A. Hushagen, Valentina Tronci, Ann-Kristin Frøyset and Kari E. Fladmark
Antioxidants 2021, 10(12), 1862; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10121862 - 23 Nov 2021
Cited by 5 | Viewed by 2152
Abstract
The eye is continuously under oxidative stress due to high metabolic activity and reactive oxygen species generated by daily light exposure. The redox-sensitive protein DJ-1 has proven to be essential in order to protect retina and retinal pigment epithelium (RPE) from oxidative-stress-induced degeneration. [...] Read more.
The eye is continuously under oxidative stress due to high metabolic activity and reactive oxygen species generated by daily light exposure. The redox-sensitive protein DJ-1 has proven to be essential in order to protect retina and retinal pigment epithelium (RPE) from oxidative-stress-induced degeneration. Here, we analyzed the specific role of Müller cell DJ-1 in the adult zebrafish retina by re-establishing Müller-cell-specific DJ-1 expression in a DJ-1 knockout retina. Loss of DJ-1 resulted in an age-dependent retinal degeneration, including loss of cells in the ganglion cell layer, retinal thinning, photoreceptor disorganization and RPE cell dysfunction. The degenerative phenotype induced by the absence of DJ-1 was inhibited by solely expressing DJ-1 in Müller cells. The protective effect was dependent upon the cysteine-106 residue of DJ-1, which has been shown to be an oxidative sensor of DJ-1. In a label-free proteomics analysis of isolated retinas, we identified proteins differentially expressed after DJ-1 knockout, but with restored levels after Müller cell DJ-1 re-insertion. Our data show that Müller cell DJ-1 has a major role in protecting the retina from age-dependent oxidative stress. Full article
(This article belongs to the Special Issue Oxidative Stress in Neurodegeneration and Neuroinflammation)
►▼ Show Figures

Figure 1

13 pages, 1759 KiB  
Article
Lipid Peroxidation Assessment in Preclinical Alzheimer Disease Diagnosis
by Carmen Peña-Bautista, Lourdes Álvarez-Sánchez, Inés Ferrer, Marina López-Nogueroles, Antonio José Cañada-Martínez, Camille Oger, Jean-Marie Galano, Thierry Durand, Miguel Baquero and Consuelo Cháfer-Pericás
Antioxidants 2021, 10(7), 1043; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10071043 - 29 Jun 2021
Cited by 13 | Viewed by 2175
Abstract
Alzheimer disease (AD) is an increasingly common neurodegenerative disease, especially in countries with aging populations. Its diagnosis is complex and is usually carried out in advanced stages of the disease. In addition, lipids and oxidative stress have been related to AD since the [...] Read more.
Alzheimer disease (AD) is an increasingly common neurodegenerative disease, especially in countries with aging populations. Its diagnosis is complex and is usually carried out in advanced stages of the disease. In addition, lipids and oxidative stress have been related to AD since the earliest stages. A diagnosis in the initial or preclinical stages of the disease could help in a more effective action of the treatments. Isoprostanoid biomarkers were determined in plasma samples from preclinical AD participants (n = 12) and healthy controls (n = 31) by chromatography and mass spectrometry (UPLC-MS/MS). Participants were accurately classified according to cerebrospinal fluid (CSF) biomarkers and neuropsychological examination. Isoprostanoid levels did not show differences between groups. However, some of them correlated with CSF biomarkers (t-tau, p-tau) and with cognitive decline. In addition, a panel including 10 biomarkers showed an area under curve (AUC) of 0.96 (0.903–1) and a validation AUC of 0.90 in preclinical AD prediction. Plasma isoprostanoids could be useful biomarkers in preclinical diagnosis for AD. However, these results would require a further validation with an external cohort. Full article
(This article belongs to the Special Issue Oxidative Stress in Neurodegeneration and Neuroinflammation)
►▼ Show Figures

Figure 1

Review

Jump to: Editorial, Research

36 pages, 6630 KiB  
Review
Vitreous Humor Proteome: Targeting Oxidative Stress, Inflammation, and Neurodegeneration in Vitreoretinal Diseases
by Fátima Milhano Santos, Joana Mesquita, João Paulo Castro-de-Sousa, Sergio Ciordia, Alberto Paradela and Cândida Teixeira Tomaz
Antioxidants 2022, 11(3), 505; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11030505 - 06 Mar 2022
Cited by 11 | Viewed by 3550
Abstract
Oxidative stress is defined as an unbalance between pro-oxidants and antioxidants, as evidenced by an increase in reactive oxygen and reactive nitrogen species production over time. It is important in the pathophysiology of retinal disorders such as diabetic retinopathy, age-related macular degeneration, retinal [...] Read more.
Oxidative stress is defined as an unbalance between pro-oxidants and antioxidants, as evidenced by an increase in reactive oxygen and reactive nitrogen species production over time. It is important in the pathophysiology of retinal disorders such as diabetic retinopathy, age-related macular degeneration, retinal detachment, and proliferative vitreoretinopathy, which are the focus of this article. Although the human organism’s defense mechanisms correct autoxidation caused by endogenous or exogenous factors, this may be insufficient, causing an imbalance in favor of excessive ROS production or a weakening of the endogenous antioxidant system, resulting in molecular and cellular damage. Furthermore, modern lifestyles and environmental factors contribute to increased chemical exposure and stress induction, resulting in oxidative stress. In this review, we discuss the current information about oxidative stress and the vitreous proteome with a special focus on vitreoretinal diseases. Additionally, we explore therapies using antioxidants in an attempt to rescue the body from oxidation, restore balance, and maximize healthy body function, as well as new investigational therapies that have shown significant therapeutic potential in preclinical studies and clinical trial outcomes, along with their goals and strategic approaches to combat oxidative stress. Full article
(This article belongs to the Special Issue Oxidative Stress in Neurodegeneration and Neuroinflammation)
►▼ Show Figures

Graphical abstract

19 pages, 753 KiB  
Review
CNS Redox Homeostasis and Dysfunction in Neurodegenerative Diseases
by Gundars Goldsteins, Vili Hakosalo, Merja Jaronen, Meike Hedwig Keuters, Šárka Lehtonen and Jari Koistinaho
Antioxidants 2022, 11(2), 405; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11020405 - 16 Feb 2022
Cited by 12 | Viewed by 4450
Abstract
A single paragraph of about 200 words maximum. Neurodegenerative diseases (ND), such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, pose a global challenge in the aging population due to the lack of treatments for their cure. Despite various disease-specific clinical symptoms, [...] Read more.
A single paragraph of about 200 words maximum. Neurodegenerative diseases (ND), such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, pose a global challenge in the aging population due to the lack of treatments for their cure. Despite various disease-specific clinical symptoms, ND have some fundamental common pathological mechanisms involving oxidative stress and neuroinflammation. The present review focuses on the major causes of central nervous system (CNS) redox homeostasis imbalance comprising mitochondrial dysfunction and endoplasmic reticulum (ER) stress. Mitochondrial disturbances, leading to reduced mitochondrial function and elevated reactive oxygen species (ROS) production, are thought to be a major contributor to the pathogenesis of ND. ER dysfunction has been implicated in ND in which protein misfolding evidently causes ER stress. The consequences of ER stress ranges from an increase in ROS production to altered calcium efflux and proinflammatory signaling in glial cells. Both pathological pathways have links to ferroptotic cell death, which has been implicated to play an important role in ND. Pharmacological targeting of these pathological pathways may help alleviate or slow down neurodegeneration. Full article
(This article belongs to the Special Issue Oxidative Stress in Neurodegeneration and Neuroinflammation)
►▼ Show Figures

Figure 1

15 pages, 689 KiB  
Review
Protection against Amyloid-β Oligomer Neurotoxicity by Small Molecules with Antioxidative Properties: Potential for the Prevention of Alzheimer’s Disease Dementia
by Wataru Araki and Fuyuki Kametani
Antioxidants 2022, 11(1), 132; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox11010132 - 07 Jan 2022
Cited by 9 | Viewed by 2550
Abstract
Soluble oligomeric assemblies of amyloid β-protein (Aβ), called Aβ oligomers (AβOs), have been recognized as primary pathogenetic factors in the molecular pathology of Alzheimer’s disease (AD). AβOs exert neurotoxicity and synaptotoxicity and play a critical role in the pathological progression of AD by [...] Read more.
Soluble oligomeric assemblies of amyloid β-protein (Aβ), called Aβ oligomers (AβOs), have been recognized as primary pathogenetic factors in the molecular pathology of Alzheimer’s disease (AD). AβOs exert neurotoxicity and synaptotoxicity and play a critical role in the pathological progression of AD by aggravating oxidative and synaptic disturbances and tau abnormalities. As such, they are important therapeutic targets. From a therapeutic standpoint, it is not only important to clear AβOs or prevent their formation, it is also beneficial to reduce their neurotoxicity. In this regard, recent studies have reported that small molecules, most with antioxidative properties, show promise as therapeutic agents for reducing the neurotoxicity of AβOs. In this mini-review, we briefly review the significance of AβOs and oxidative stress in AD and summarize studies on small molecules with AβO-neurotoxicity-reducing effects. We also discuss mechanisms underlying the effects of these compounds against AβO neurotoxicity as well as their potential as drug candidates for the prevention and treatment of AD. Full article
(This article belongs to the Special Issue Oxidative Stress in Neurodegeneration and Neuroinflammation)
►▼ Show Figures

Figure 1

25 pages, 1093 KiB  
Review
Role of Oxidative Stress in Ocular Diseases Associated with Retinal Ganglion Cells Degeneration
by Eugene Yu-Chuan Kang, Pei-Kang Liu, Yao-Tseng Wen, Peter M. J. Quinn, Sarah R. Levi, Nan-Kai Wang and Rong-Kung Tsai
Antioxidants 2021, 10(12), 1948; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10121948 - 05 Dec 2021
Cited by 35 | Viewed by 5278
Abstract
Ocular diseases associated with retinal ganglion cell (RGC) degeneration is the most common neurodegenerative disorder that causes irreversible blindness worldwide. It is characterized by visual field defects and progressive optic nerve atrophy. The underlying pathophysiology and mechanisms of RGC degeneration in several ocular [...] Read more.
Ocular diseases associated with retinal ganglion cell (RGC) degeneration is the most common neurodegenerative disorder that causes irreversible blindness worldwide. It is characterized by visual field defects and progressive optic nerve atrophy. The underlying pathophysiology and mechanisms of RGC degeneration in several ocular diseases remain largely unknown. RGCs are a population of central nervous system neurons, with their soma located in the retina and long axons that extend through the optic nerve to form distal terminals and connections in the brain. Because of this unique cytoarchitecture and highly compartmentalized energy demand, RGCs are highly mitochondrial-dependent for adenosine triphosphate (ATP) production. Recently, oxidative stress and mitochondrial dysfunction have been found to be the principal mechanisms in RGC degeneration as well as in other neurodegenerative disorders. Here, we review the role of oxidative stress in several ocular diseases associated with RGC degenerations, including glaucoma, hereditary optic atrophy, inflammatory optic neuritis, ischemic optic neuropathy, traumatic optic neuropathy, and drug toxicity. We also review experimental approaches using cell and animal models for research on the underlying mechanisms of RGC degeneration. Lastly, we discuss the application of antioxidants as a potential future therapy for the ocular diseases associated with RGC degenerations. Full article
(This article belongs to the Special Issue Oxidative Stress in Neurodegeneration and Neuroinflammation)
►▼ Show Figures

Figure 1

21 pages, 6286 KiB  
Review
TRAP1 in Oxidative Stress and Neurodegeneration
by Inês Ramos Rego, Beatriz Santos Cruz, António Francisco Ambrósio and Celso Henrique Alves
Antioxidants 2021, 10(11), 1829; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10111829 - 19 Nov 2021
Cited by 13 | Viewed by 4524
Abstract
Tumor necrosis factor receptor-associated protein 1 (TRAP1), also known as heat shock protein 75 (HSP75), is a member of the heat shock protein 90 (HSP90) chaperone family that resides mainly in the mitochondria. As a mitochondrial molecular chaperone, TRAP1 supports protein folding and [...] Read more.
Tumor necrosis factor receptor-associated protein 1 (TRAP1), also known as heat shock protein 75 (HSP75), is a member of the heat shock protein 90 (HSP90) chaperone family that resides mainly in the mitochondria. As a mitochondrial molecular chaperone, TRAP1 supports protein folding and contributes to the maintenance of mitochondrial integrity even under cellular stress. TRAP1 is a cellular regulator of mitochondrial bioenergetics, redox homeostasis, oxidative stress-induced cell death, apoptosis, and unfolded protein response (UPR) in the endoplasmic reticulum (ER). TRAP1 has attracted increasing interest as a therapeutical target, with a special focus on the design of TRAP1 specific inhibitors. Although TRAP1 was extensively studied in the oncology field, its role in central nervous system cells, under physiological and pathological conditions, remains largely unknown. In this review, we will start by summarizing the biology of TRAP1, including its structure and related pathways. Thereafter, we will continue by debating the role of TRAP1 in the maintenance of redox homeostasis and protection against oxidative stress and apoptosis. The role of TRAP1 in neurodegenerative disorders will also be discussed. Finally, we will review the potential of TRAP1 inhibitors as neuroprotective drugs. Full article
(This article belongs to the Special Issue Oxidative Stress in Neurodegeneration and Neuroinflammation)
►▼ Show Figures

Figure 1

15 pages, 2095 KiB  
Review
Bisretinoids of the Retina: Photo-Oxidation, Iron-Catalyzed Oxidation, and Disease Consequences
by Hye Jin Kim, Diego Montenegro, Jin Zhao and Janet R. Sparrow
Antioxidants 2021, 10(9), 1382; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10091382 - 29 Aug 2021
Cited by 17 | Viewed by 2514
Abstract
The retina and, in particular, retinal pigment epithelial cells are unusual for being encumbered by exposure to visible light, while being oxygen-rich, and also amassing photoreactive molecules. These fluorophores (bisretinoids) are generated as a byproduct of the activity of vitamin A aldehyde—the chromophore [...] Read more.
The retina and, in particular, retinal pigment epithelial cells are unusual for being encumbered by exposure to visible light, while being oxygen-rich, and also amassing photoreactive molecules. These fluorophores (bisretinoids) are generated as a byproduct of the activity of vitamin A aldehyde—the chromophore necessary for vision. Bisretinoids form in photoreceptor cells due to random reactions of two molecules of vitamin A aldehyde with phosphatidylethanolamine; bisretinoids are subsequently transferred to retinal pigment epithelial (RPE) cells, where they accumulate in the lysosomal compartment with age. Bisretinoids can generate reactive oxygen species by both energy and electron transfer, and they become photo-oxidized and photolyzed in the process. While these fluorescent molecules are accrued by RPE cells of all healthy eyes, they are also implicated in retinal disease. Full article
(This article belongs to the Special Issue Oxidative Stress in Neurodegeneration and Neuroinflammation)
►▼ Show Figures

Figure 1

28 pages, 2522 KiB  
Review
Human Paraoxonase-2 (PON2): Protein Functions and Modulation
by Giuseppe Manco, Elena Porzio and Teresa Maria Carusone
Antioxidants 2021, 10(2), 256; https://0-doi-org.brum.beds.ac.uk/10.3390/antiox10020256 - 07 Feb 2021
Cited by 32 | Viewed by 5845
Abstract
PON1, PON2, and PON3 belong to a family of lactone hydrolyzing enzymes endowed with various substrate specificities. Among PONs, PON2 shows the highest hydrolytic activity toward many acyl-homoserine lactones (acyl-HL) involved in bacterial quorum-sensing signaling. Accordingly, defense against pathogens, such as Brevundimonas aeruginosa [...] Read more.
PON1, PON2, and PON3 belong to a family of lactone hydrolyzing enzymes endowed with various substrate specificities. Among PONs, PON2 shows the highest hydrolytic activity toward many acyl-homoserine lactones (acyl-HL) involved in bacterial quorum-sensing signaling. Accordingly, defense against pathogens, such as Brevundimonas aeruginosa (B. aeruginosa), was postulated to be the principal function of PON2. However, recent findings have highlighted the importance of PON2 in oxidative stress control, inhibition of apoptosis, and the progression of various types of malignancies. This review focuses on all of these aspects of PON2. Full article
(This article belongs to the Special Issue Oxidative Stress in Neurodegeneration and Neuroinflammation)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-15
Back to TopTop