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Antioxidants
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Mitochondrial Dysfunction and Oxidative Stress in the Pathogenesis of Neurodegenerative...
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Mitochondrial Dysfunction and Oxidative Stress in the Pathogenesis of Neurodegenerative Disease

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 January 2024) | Viewed by 10650

Special Issue Editors

Dr. Marco Bisaglia

E-Mail Website
Guest Editor
Department of Biology, University of Padova, Via Ugo Bassi 58/B, 35131 Padova, Italy
Interests: neurodegenerative disease; mitochondrial dysfunction; oxidative stress; Parkinson’s diseases; molecular mechanisms
Prof. Dr. Sasanka Chakrabarti

E-Mail Website
Guest Editor
Department of Biochemistry and Central Research Cell, Maharishi Markandeshwar Institute of Medical Sciences and Research, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala 133207, India
Interests: mitochondria; neurodegenerative diseases; cell biology; oxidative stress

Special Issue Information

Dear Colleagues,

Neurodegenerative diseases are a heterogeneous group of disorders characterized by the progressive degeneration of neuronal cells. While the etiopathogenesis of these disorders is still elusive, they usually share common pathological features, and increasing evidence now exists that supports the interplay between mitochondrial dysfunctions and oxidative stress as contributing factors in the onset and progression of most neurodegenerative diseases.

Due to its high oxygen consumption, low antioxidant defenses, and high content of metal ions and polyunsaturated lipids, the brain is particularly sensitive to oxidative injury. Mitochondrial alterations, including calcium dyshomeostasis, impairment in the mitochondrial quality-control process, decreased mitochondrial bioenergetic capacity, and defects in the mitochondrial respiratory chain complexes, have been often described as key events in neurodegeneration, and they can dramatically increase the production of reactive oxygen species. At the same time, free radical species have been demonstrated to affect mitochondrial functionality. In fact, mitochondrial dysfunction and oxidative stress are interdependent processes, which are linked to several regulated cell death pathways involved in neurodegenerative diseases.

The aim of this Special Issue is to provide a broad and updated overview of the involvement of mitochondrial dysfunction and oxidative stress in different neurodegenerative disorders, with particular emphasis on cellular and molecular aspects, novel potential therapeutic approaches, and suitable experimental models. Since mitochondria diseases are often associated with neuronal phenotypes, papers concerning this specific class of disorders are also welcome. Reviews and original research articles that cover any pertinent topic in the fields mentioned above, both basic and clinical aspects, will be considered.

Dr. Marco Bisaglia
Prof. Dr. Sasanka Chakrabarti
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

  • Alzheimer disease
  • amyotrophic lateral sclerosis
  • ferroptosis
  • Friedreich ataxia
  • Huntington disease
  • iron
  • mitochondria disorders
  • mitochondria dysfunction
  • neurodegeneration
  • oxidative stress
  • Parkinson’s disease
  • reactive oxygen species

Published Papers (5 papers)

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Research

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25 pages, 6338 KiB  
Article
Glycine-Alanine Dipeptide Repeat Protein from C9-ALS Interacts with Sulfide Quinone Oxidoreductase (SQOR) to Induce the Activity of the NLRP3 Inflammasome in HMC3 Microglia: Irisflorentin Reverses This Interaction
by Ru-Huei Fu, Hui-Jye Chen and Syuan-Yu Hong
Antioxidants 2023, 12(10), 1896; https://doi.org/10.3390/antiox12101896 - 23 Oct 2023
Cited by 2 | Viewed by 1324
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal rare disease of progressive degeneration of motor neurons. The most common genetic mutation in ALS is the hexanucleotide repeat expansion (HRE) located in the first intron of the C9orf72 gene (C9-ALS). HRE can produce dipeptide repeat [...] Read more.
Amyotrophic lateral sclerosis (ALS) is a fatal rare disease of progressive degeneration of motor neurons. The most common genetic mutation in ALS is the hexanucleotide repeat expansion (HRE) located in the first intron of the C9orf72 gene (C9-ALS). HRE can produce dipeptide repeat proteins (DPRs) such as poly glycine-alanine (GA) in a repeat-associated non-ATG (RAN) translation. GA-DPR has been shown to be toxic to motor neurons in various biological models. However, its effects on microglia involved in C9-ALS have not been reported. Here, we show that GA-DPR (GA50) activates the NLR family pyrin domain containing 3 (NLRP3) inflammasome in a human HMC3 microglia model. MCC950 (specific inhibitor of the NLRP3) treatment can abrogate this activity. Next, using yeast two-hybrid screening, we identified sulfide quinone oxidoreductase (SQOR) as a GA50 interacting protein. SQOR knockdown in HMC3 cells can significantly induce the activity of the NLRP3 inflammasome by upregulating the level of intracellular reactive oxygen species and the cytoplasmic escape of mitochondrial DNA. Furthermore, we obtained irisflorentin as an effective blocker of the interaction between SQOR and GA50, thus inhibiting NLRP3 inflammasome activity in GA50-expressing HMC3 cells. These results imply the association of GA-DPR, SQOR, and NLRP3 inflammasomes in microglia and establish a treatment strategy for C9-ALS with irisflorentin. Full article
(This article belongs to the Special Issue Mitochondrial Dysfunction and Oxidative Stress in the Pathogenesis of Neurodegenerative Disease)
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Review

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21 pages, 1069 KiB  
Review
Exosomal Dynamics and Brain Redox Imbalance: Implications in Alzheimer’s Disease Pathology and Diagnosis
by Aritri Bir, Arindam Ghosh, Aman Chauhan, Sarama Saha, Adesh K. Saini, Marco Bisaglia and Sasanka Chakrabarti
Antioxidants 2024, 13(3), 316; https://doi.org/10.3390/antiox13030316 - 05 Mar 2024
Viewed by 1559
Abstract
Oxidative burden plays a central role in Alzheimer’s disease (AD) pathology, fostering protein aggregation, inflammation, mitochondrial impairment, and cellular dysfunction that collectively lead to neuronal injury. The role of exosomes in propagating the pathology of neurodegenerative diseases including AD is now well established. [...] Read more.
Oxidative burden plays a central role in Alzheimer’s disease (AD) pathology, fostering protein aggregation, inflammation, mitochondrial impairment, and cellular dysfunction that collectively lead to neuronal injury. The role of exosomes in propagating the pathology of neurodegenerative diseases including AD is now well established. However, recent studies have also shown that exosomes are crucial responders to oxidative stress in different tissues. Thus, this offers new insights and mechanistic links within the complex pathogenesis of AD through the involvement of oxidative stress and exosomes. Several studies have indicated that exosomes, acting as intracellular communicators, disseminate oxidatively modified contents from one cell to another, propagating the pathology of AD. Another emerging aspect is the exosome-mediated inhibition of ferroptosis in multiple tissues under different conditions which may have a role in neurodegenerative diseases as well. Apart from their involvement in the pathogenesis of AD, exosomes enter the bloodstream serving as novel noninvasive biomarkers for AD; some of the exosome contents also reflect the cerebral oxidative stress in this disease condition. This review highlights the intricate interplay between oxidative stress and exosome dynamics and underscores the potential of exosomes as a novel tool in AD diagnosis. Full article
(This article belongs to the Special Issue Mitochondrial Dysfunction and Oxidative Stress in the Pathogenesis of Neurodegenerative Disease)
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19 pages, 2469 KiB  
Review
Mitochondria Dysfunction and Neuroinflammation in Neurodegeneration: Who Comes First?
by Caterina Peggion, Tito Calì and Marisa Brini
Antioxidants 2024, 13(2), 240; https://doi.org/10.3390/antiox13020240 - 16 Feb 2024
Viewed by 2153
Abstract
Neurodegenerative diseases (NDs) encompass an assorted array of disorders such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, each characterised by distinct clinical manifestations and underlying pathological mechanisms. While some cases have a genetic basis, many NDs occur sporadically. Despite their differences, [...] Read more.
Neurodegenerative diseases (NDs) encompass an assorted array of disorders such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, each characterised by distinct clinical manifestations and underlying pathological mechanisms. While some cases have a genetic basis, many NDs occur sporadically. Despite their differences, these diseases commonly feature chronic neuroinflammation as a hallmark. Consensus has recently been reached on the possibility that mitochondria dysfunction and protein aggregation can mutually contribute to the activation of neuroinflammatory response and thus to the onset and progression of these disorders. In the present review, we discuss the contribution of mitochondria dysfunction and neuroinflammation to the aetiology and progression of NDs, highlighting the possibility that new potential therapeutic targets can be identified to tackle neurodegenerative processes and alleviate the progression of these pathologies. Full article
(This article belongs to the Special Issue Mitochondrial Dysfunction and Oxidative Stress in the Pathogenesis of Neurodegenerative Disease)
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18 pages, 1613 KiB  
Review
Effects of Redox Homeostasis and Mitochondrial Damage on Alzheimer’s Disease
by Yi-Hsuan Wu and Hsi-Lung Hsieh
Antioxidants 2023, 12(10), 1816; https://doi.org/10.3390/antiox12101816 - 30 Sep 2023
Cited by 2 | Viewed by 1378
Abstract
Bioenergetic mitochondrial dysfunction is a common feature of several diseases, including Alzheimer’s disease (AD), where redox imbalance also plays an important role in terms of disease development. AD is an age-related disease and begins many years before the appearance of neurodegenerative symptoms. Intracellular [...] Read more.
Bioenergetic mitochondrial dysfunction is a common feature of several diseases, including Alzheimer’s disease (AD), where redox imbalance also plays an important role in terms of disease development. AD is an age-related disease and begins many years before the appearance of neurodegenerative symptoms. Intracellular tau aggregation, extracellular β-amyloid (Aβ) deposition in the brain, and even the APOE4 genotype contribute to the process of AD by impairing redox homeostasis and mitochondrial dysfunction. This review summarizes the evidence for the redox imbalance and mitochondrial dysfunction in AD and demonstrates the current therapeutic strategies related to mitochondrial maintenance. Full article
(This article belongs to the Special Issue Mitochondrial Dysfunction and Oxidative Stress in the Pathogenesis of Neurodegenerative Disease)
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22 pages, 1379 KiB  
Review
Lactate: A Theranostic Biomarker for Metabolic Psychiatry?
by Edward Caddye, Julien Pineau, Joshua Reyniers, Itamar Ronen and Alessandro Colasanti
Antioxidants 2023, 12(9), 1656; https://doi.org/10.3390/antiox12091656 - 22 Aug 2023
Cited by 1 | Viewed by 3781
Abstract
Alterations in neurometabolism and mitochondria are implicated in the pathophysiology of psychiatric conditions such as mood disorders and schizophrenia. Thus, developing objective biomarkers related to brain mitochondrial function is crucial for the development of interventions, such as central nervous system penetrating agents that [...] Read more.
Alterations in neurometabolism and mitochondria are implicated in the pathophysiology of psychiatric conditions such as mood disorders and schizophrenia. Thus, developing objective biomarkers related to brain mitochondrial function is crucial for the development of interventions, such as central nervous system penetrating agents that target brain health. Lactate, a major circulatory fuel source that can be produced and utilized by the brain and body, is presented as a theranostic biomarker for neurometabolic dysfunction in psychiatric conditions. This concept is based on three key properties of lactate that make it an intriguing metabolic intermediate with implications for this field: Firstly, the lactate response to various stimuli, including physiological or psychological stress, represents a quantifiable and dynamic marker that reflects metabolic and mitochondrial health. Second, lactate concentration in the brain is tightly regulated according to the sleep–wake cycle, the dysregulation of which is implicated in both metabolic and mood disorders. Third, lactate universally integrates arousal behaviours, pH, cellular metabolism, redox states, oxidative stress, and inflammation, and can signal and encode this information via intra- and extracellular pathways in the brain. In this review, we expand on the above properties of lactate and discuss the methodological developments and rationale for the use of functional magnetic resonance spectroscopy for in vivo monitoring of brain lactate. We conclude that accurate and dynamic assessment of brain lactate responses might contribute to the development of novel and personalized therapies that improve mitochondrial health in psychiatric disorders and other conditions associated with neurometabolic dysfunction. Full article
(This article belongs to the Special Issue Mitochondrial Dysfunction and Oxidative Stress in the Pathogenesis of Neurodegenerative Disease)
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