Crosstalk between mitochondrial dysfunction, oxidative stress, and age related neurodegenerative disease: Etiologies and therapeutic strategies

RNA binding proteins fulfil a wide number of roles in gene expression. Multiple mechanisms of RNA binding protein dysregulation have been implicated in the pathomechanisms of several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Oxidative stress and mitochondrial dysfunction also play important roles in these diseases. In this review, we highlight the mechanistic interplay between RNA binding protein dysregulation, oxidative stress and mitochondrial dysfunction in ALS. We also discuss different potential therapeutic strategies targeting these pathways.

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Age-Related Macular Degeneration: Role of Oxidative Stress and Blood Vessels

International Journal of Molecular Sciences ◽

10.3390/ijms22031296 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1296

Author(s):

Yue Ruan ◽

Subao Jiang ◽

Adrian Gericke

Keyword(s):

Oxidative Stress ◽

Macular Degeneration ◽

Vascular Function ◽

Vascular Dysfunction ◽

Therapeutic Strategies ◽

Vision Impairment ◽

Age Related Macular Degeneration ◽

Oxygen Species ◽

Age Related

Age-related macular degeneration (AMD) is a common irreversible ocular disease characterized by vision impairment among older people. Many risk factors are related to AMD and interact with each other in its pathogenesis. Notably, oxidative stress and choroidal vascular dysfunction were suggested to be critically involved in AMD pathogenesis. In this review, we give an overview on the factors contributing to the pathophysiology of this multifactorial disease and discuss the role of reactive oxygen species and vascular function in more detail. Moreover, we give an overview on therapeutic strategies for patients suffering from AMD.

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Low-Dose Ionizing Radiation Therapy: A Novel Treatment for Post-Concussion Syndrome?

Dose-Response ◽

10.1177/15593258211044341 ◽

2021 ◽

Vol 19 (4) ◽

pp. 155932582110443

Author(s):

Paul A. Oakley

Keyword(s):

Oxidative Stress ◽

Radiation Therapy ◽

Ionizing Radiation ◽

Neurodegenerative Disease ◽

Low Dose ◽

Post Injury ◽

Post Concussion Syndrome ◽

Persistent Symptoms ◽

Age Related ◽

Alzhiemer's Disease

A subset of victims who experience concussion suffer from persistent symptoms spanning months to years post-injury, termed post-concussion syndrome (PCS). Problematically, there is lack of consensus for the treatment of PCS. Concussion injury involves a neurometabolic cascade leading to oxidative stress and neuroinflammation which parallels the oxidative stress loading occuring from age-related neurodegenerative conditions. Historical and recent evidence has emerged showing the efficacy of low-dose radiation therapy for many human diseases including neurodegenerative diseases such as Alzhiemer’s disease (AD). Due to the pathognomonic similarities of oxidative stress and neuroinflammation involved in PCS and neurodegenerative disease, treatments that prove successful for neurodegenerative disease may prove successful for PCS. Recently, low-dose ionizing radiation therapy (LDIR) has been documented to show a reversal of many symptoms in AD, including improved cognition. LDIR is thought to induce a switching from proinflammatory M1 phenotype to an anti-inflammatory M2 phenotype. In other words, a continual upregulation of the adaptive protection systems via LDIR induces health enhancement. It is hypothesized LDIR treatment for PCS would mimic that seen from early evidence of LDIR treatment of AD patients who suffer from similar oxidative stress loading. We propose the application of LDIR is a promising, untapped treatment for PCS.

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Honeybush Extracts (Cyclopia spp.) Rescue Mitochondrial Functions and Bioenergetics against Oxidative Injury

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/1948602 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Anastasia Agapouda ◽

Veronika Butterweck ◽

Matthias Hamburger ◽

Dalene de Beer ◽

Elizabeth Joubert ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

Hot Water ◽

Human Neuroblastoma ◽

Atp Production ◽

Physiological Conditions ◽

Age Related ◽

Mitochondrial Functions ◽

Scientific Attention

Mitochondrial dysfunction plays a major role not only in the pathogenesis of many oxidative stress or age-related diseases such as neurodegenerative as well as mental disorders but also in normal aging. There is evidence that oxidative stress and mitochondrial dysfunction are the most upstream and common events in the pathomechanisms of neurodegeneration. Cyclopia species are endemic South African plants and some have a long tradition of use as herbal tea, known as honeybush tea. Extracts of the tea are gaining more scientific attention due to their phenolic composition. In the present study, we tested not only the in vitro mitochondria-enhancing properties of honeybush extracts under physiological conditions but also their ameliorative properties under oxidative stress situations. Hot water and ethanolic extracts of C. subternata, C. genistoides, and C. longifolia were investigated. Pretreatment of human neuroblastoma SH-SY5Y cells with honeybush extracts, at a concentration range of 0.1-1 ng/ml, had a beneficial effect on bioenergetics as it increased ATP production, respiration, and mitochondrial membrane potential (MMP) after 24 hours under physiological conditions. The aqueous extracts of C. subternata and C. genistoides, in particular, showed a protective effect by rescuing the bioenergetic and mitochondrial deficits under oxidative stress conditions (400 μM H2O2 for 3 hours). These findings indicate that honeybush extracts could constitute candidates for the prevention of oxidative stress with an impact on aging processes and age-related neurodegenerative disorders potentially leading to the development of a condition-specific nutraceutical.

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Mitochondria-Targeted Antioxidants for Treatment of Hearing Loss: A Systematic Review

Antioxidants ◽

10.3390/antiox8040109 ◽

2019 ◽

Vol 8 (4) ◽

pp. 109 ◽

Cited By ~ 14

Author(s):

Chisato Fujimoto ◽

Tatsuya Yamasoba

Keyword(s):

Oxidative Stress ◽

Hearing Loss ◽

Mitochondrial Dysfunction ◽

Cell Lines ◽

Mitochondrial Gene ◽

Protective Effects ◽

Drug Induced ◽

Age Related ◽

Cochlear Damage ◽

Age Related Hearing Loss

Mitochondrial dysfunction is associated with the etiologies of sensorineural hearing loss, such as age-related hearing loss, noise- and ototoxic drug-induced hearing loss, as well as hearing loss due to mitochondrial gene mutation. Mitochondria are the main sources of reactive oxygen species (ROS) and ROS-induced oxidative stress is involved in cochlear damage. Moreover, the release of ROS causes further damage to mitochondrial components. Antioxidants are thought to counteract the deleterious effects of ROS and thus, may be effective for the treatment of oxidative stress-related diseases. The administration of mitochondria-targeted antioxidants is one of the drug delivery systems targeted to mitochondria. Mitochondria-targeted antioxidants are expected to help in the prevention and/or treatment of diseases associated with mitochondrial dysfunction. Of the various mitochondria-targeted antioxidants, the protective effects of MitoQ and SkQR1 against ototoxicity have been previously evaluated in animal models and/or mouse auditory cell lines. MitoQ protects against both gentamicin- and cisplatin-induced ototoxicity. SkQR1 also provides auditory protective effects against gentamicin-induced ototoxicity. On the other hand, decreasing effect of MitoQ on gentamicin-induced cell apoptosis in auditory cell lines has been controversial. No clinical studies have been reported for otoprotection using mitochondrial-targeted antioxidants. High-quality clinical trials are required to reveal the therapeutic effect of mitochondria-targeted antioxidants in terms of otoprotection in patients.

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The role of mitochondria-targeted antioxidant MitoQ in neurodegenerative disease

Molecular and Cellular Therapies ◽

10.13052/2052-8426-2018-01 ◽

2018 ◽

pp. 1-8

Author(s):

Linlin Zhang ◽

Aurelio Reyes ◽

Xiangdong Wang

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neurodegenerative Diseases ◽

Mitochondrial Dysfunction ◽

Neurodegenerative Disease ◽

Amyloid Β ◽

Amyloid Β Peptide ◽

And Oxidative Stress

Abstract: The discovery of charged molecules being able to cross the mitochondrial membrane has prompted many scholars to exploit this idea to find a way of preventing or slowing down aging. In this paper, we will focus on mitochondriatargeted antioxidants, which are cationic derivatives of plastoquinone, and in particular on the mitochondria-targeted antioxidant therapy of neurodegenerative diseases. It is well known that the accumulation of amyloid-β peptide (Aβ) in mitochondria and its related mitochondrial dysfunction are critical signatures of Alzheimer’ s disease (AD). In another neurodegenerative disease, Parkinson’s disease (PD), the loss of dopaminergic neurons in the substantia nigra and the production of Lewy bodies are among their pathological features. Pathogenesis of Parkinson’s disease and Alzheimer’s disease has been frequently linked to mitochondrial dysfunction and oxidative stress. Recent studies show that MitoQ, a mitochondria-targeted antioxidant, may possess therapeutic potential for Aβ-related and oxidative stress-associated neurodegenerative diseases, especially AD. Although MitoQ has been developed to the stage of clinical trials in PD, its true clinical effect still need further verification. This review aims to discuss the role of mitochondrial pathology in neurodegenerative diseases, as well as the recent development of mitochondrial targeted antioxidants as a potential treatment for these diseases by removing excess oxygen free radicals and inhibiting lipid peroxidation in order to improve mitochondrial function.

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Improved Effect of a Mitochondria-Targeted Antioxidant on Hydrogen Peroxide-Induced Oxidative Stress in Human Retinal Pigment Epithelium Cells

10.21203/rs.3.rs-37398/v1 ◽

2020 ◽

Author(s):

MYUNG HEE KIM ◽

Dae Hyun Kim ◽

Su Geun Yang ◽

Dae Yu Kim

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

Transcription Factors ◽

Mitochondrial Dysfunction ◽

Retinal Pigment ◽

Protective Role ◽

Age Related Macular Degeneration ◽

Ros Generation ◽

Rpe Cells ◽

Age Related

Abstract Background: Oxidative damage in retinal pigmented epithelium (RPE) cells contributes to the development of age-related macular degeneration, which is among the leading causes of visual loss in elderly people. In the present study, we evaluated the protective role of TPP-Niacin against the hydrogen peroxide (H2O2)-induced oxidative stress to RPE cells. Methods: The cellular viability, lactate dehydrogenase, reactive oxygen species (ROS), and mitochondrial function were determined in the retinal ARPE-19 cells under the treatment with H2O2 or pre-treatment with TPP-Niacin. The expression level of mitochondrial related genes and some transcription factors were assessed using real-time polymerase chain reaction (RT-PCR). Results: TPP-Niacin significantly improved cell viability reduction, reduced ROS generation and increased the antioxidant enzymes in H2O2-treated ARPE-19 cells. Mitochondrial dysfunction from H2O2-induced oxidative stress was also significantly diminished by the TPP-Niacin treatment, reduced generation of ROS, an ameliorated reduction of mitochondrial membrane potential (MMP) and an upregulated mitochondrial associated gene. In addition, TPP-Niacin markedly enhanced the expression of transcription factors (PGC-1α and NRF2) and antioxidant associated genes (especially, HO-1 and NQO-1). Conclusion: We proved the protective effect of TPP-Niacin against H2O2-induced oxidative stress in RPE cells. TPP-Niacin is believed to have played a protective role against mitochondrial dysfunction by up-regulating antioxidant-related genes such as PGC-1α, NRF2, HO-1 and NQO-1 in RPE cells.

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Metformin alleviates stress-induced cellular senescence of aging human adipose stromal cells and the ensuing adipocyte dysfunction

eLife ◽

10.7554/elife.62635 ◽

2021 ◽

Vol 10 ◽

Author(s):

Laura Le Pelletier ◽

Matthieu Mantecon ◽

Jennifer Gorwood ◽

Martine Auclair ◽

Roberta Foresti ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Sensitivity ◽

Mitochondrial Dysfunction ◽

Stromal Cells ◽

Subcutaneous Fat ◽

Normal Weight ◽

Young Donor ◽

Age Related ◽

Aged Donor

Aging is associated with central fat redistribution and insulin resistance. To identify age-related adipose features, we evaluated the senescence and adipogenic potential of adipose-derived-stromal cells (ASCs) from abdominal subcutaneous fat obtained from healthy normal-weight young (<25y) or older women (>60y). Increased cell passages of young-donor ASCs (in vitro aging), resulted in senescence but not oxidative stress. ASC-derived adipocytes presented impaired adipogenesis but no early mitochondrial dysfunction. Conversely, aged-donor ASCs at early passages displayed oxidative stress and mild senescence. ASC-derived adipocytes exhibited oxidative stress, and early mitochondrial dysfunction but adipogenesis was preserved. In vitro aging of aged-donor ASCs resulted in further increased senescence, mitochondrial dysfunction, oxidative stress and severe adipocyte dysfunction. When in vitro aged young-donor ASCs were treated with metformin, no alteration was alleviated. Conversely, metformin treatment of aged-donor ASCs decreased oxidative stress and mitochondrial dysfunction resulting in decreased senescence. Metformin's prevention of oxidative stress and of the resulting senescence improved the cells' adipogenic capacity and insulin sensitivity. This effect was mediated by the activation of AMP-activated-protein-kinase as revealed by its specific inhibition and activation. Overall, aging ASC-derived adipocytes presented impaired adipogenesis and insulin sensitivity. Targeting stress-induced senescence of ASCs with metformin may improve age-related adipose tissue dysfunction.

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