Effects of Multifunctional Antioxidants on Mitochondrial Dysfunction and Amyloid-β Metal Dyshomeostasis

Kawada, Hiroyoshi; Blessing, K.; Kiyota, Tomomi; Woolman, Theodor A; Winchester, Lee C.; Kador, Peter F.

doi:10.3233/jad-132471

Cited by 18 publications

(11 citation statements)

References 44 publications

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“…Oxidative stress is the mediator of apoptosis caused by A β [ 29 , 30 ]. Oxidative stress refers to the imbalance between oxidation and antioxidation in the body that causes excessive ROS production in the body, resulting in cell and tissue damage [ 31 , 32 ]. As the main indicator of oxidative stress level, ROS can damage nucleic acids and proteins by attacking fatty acids on cell membranes to produce peroxides, triggering inflammation and apoptosis to accelerate aging.…”

Section: Dissussionmentioning

confidence: 99%

Protective Effects and Mechanisms of Dendrobium nobile Lindl. Alkaloids on PC12 Cell Damage Induced by Aβ25-35

Liu

Yang

et al. 2021

Behavioural Neurology

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Background. Aβ deposition abnormally in the mitochondria can damage the mitochondrial respiratory chain and activate the mitochondrial-mediated apoptosis pathway, resulting in AD-like symptoms. Objective. To observe the protective effects of Dendrobium nobile Lindl. alkaloids (DNLA) on Aβ25-35-induced oxidative stress and apoptosis in PC12 cells explore its possible protective mechanisms. Methods. PC12 cells were treated with DNLA with different concentrations (0.035 mg/L, 0.3 mg/L, and 3.5 mg/L) for 6 h, followed by administration with Aβ25-35 (10 μM) for 24 h. MTT assay and flow cytometer observe the effect of DNLA on Aβ25-35-induced cytotoxicity and apoptosis of PC12 cell. Based on the mitochondrial apoptosis pathway to study the antiapoptotic effect of DNLA on this model and its relationship with oxidative stress, flow cytometer detected the level of reactive oxygen species (ROS), and ELISA kits were used to detect superoxide dismutase activity (SOD) and glutathione (GSH) content in cells. The JC-1 fluorescent staining observed the effect of DNLA on the mitochondrial membrane potential (MMP) with inverted immunofluorescence microscopy. Western blot was used to detect the levels of mitochondrial apoptosis pathway-related protein and its major downstream proteins Bax, Bcl-2, cleaved-caspase-9, and cleaved-caspase-3. Results. DNLA can significantly improve the viability and apoptosis rate of PC12 cell damage induced by Aβ25-35. It also can restore the reduced intracellular ROS content and MMP, while SOD activity and GSH content increase significantly. The expression of apoptosis-related protein Bax, cleaved-caspase-9, and cleaved-caspase-3 decreased when the Bcl-2 protein expression was significantly increased. Conclusion. These findings suggest that it can significantly inhibit the apoptosis of PC12 cell damage induced by Aβ25-35. The mechanism may reduce the level of cellular oxidative stress and thus inhibit the mitochondrial-mediated apoptosis pathway.

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Section: Dissussionmentioning

confidence: 99%

Protective Effects and Mechanisms of Dendrobium nobile Lindl. Alkaloids on PC12 Cell Damage Induced by Aβ25-35

Liu

Yang

et al. 2021

Behavioural Neurology

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“…Interestingly, recent evidence suggests that HK-2, a multifunctional antioxidant with a metal chelator and free radical scavenger properties (Kawada and Kador, 2015 ; Kawada et al, 2015 ; Chen et al, 2020 ), is effective in treating NIHL. Oral administration of HK-2 to Sprague-Dawley rats 10 days before noise over-exposure exerts a significant protective effect in the cochlea, not only enhancing hair cell survival but also reducing the auditory threshold shifts when compared to untreated rats.…”

Section: Oxidative Stress and Antioxidantsmentioning

confidence: 99%

Antioxidants and Vasodilators for the Treatment of Noise-Induced Hearing Loss: Are They Really Effective?

Alvarado

Fuentes–Santamaría

Juı́z

2020

Front. Cell. Neurosci.

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We live in a world continuously immersed in noise, an environmental, recreational, and occupational factor present in almost every daily human activity. Exposure to high-level noise could affect the auditory function of individuals at any age, resulting in a condition called noise-induced hearing loss (NIHL). Given that by 2018, more than 400 million people worldwide were suffering from disabling hearing loss and that about one-third involved noise over-exposure, which represents more than 100 million people, this hearing impairment represents a serious health problem. As of today, there are no therapeutic measures available to treat NIHL. Conventional preventive measures, including public awareness and education and physical barriers to noise, do not seem to suffice, as the population is still being affected by damaging noise levels. Therefore, it is necessary to develop or test pharmacological agents that may prevent and/or diminish the impact of noise on hearing. Data availability about the pathophysiological processes involved in triggering NIHL has allowed researchers to use compounds, that could act as effective therapies, by targeting specific mechanisms such as the excess generation of free radicals and blood flow restriction to the cochlea. In this review, we summarize the advantages/disadvantages of these therapeutic agents, providing a critical view of whether they could be effective in the human clinic.

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“…The challenge of testing such intricate and open-end hypotheses scenery, is the complexity and multiplicity of factors involved in the genesis and development of both neurodegenerative conditions. Frailty and related oxidative stress have recently drawn considerable attention ( Kawada et al, 2015 ; Panza et al, 2015a , b ; Huang et al, 2016 ; Shen et al, 2018 ; Wang and Puel, 2020 ; Misrani et al, 2021 ). In this review, we discuss the possibility that the oxidative stress linked to frailty, could be, at least in part, primarily involved in the interplay between ARHL and AD.…”

Section: Introduction: the Neurobiological Missing Links Between Age-related Hearing Loss And Alzheimer’s Diseasementioning

confidence: 99%

Frailty Syndrome and Oxidative Stress as Possible Links Between Age-Related Hearing Loss and Alzheimer’s Disease

2022

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As it is well known, a worldwide improvement in life expectancy has taken place. This has brought an increase in chronic pathologies associated with aging. Cardiovascular, musculoskeletal, psychiatric, and neurodegenerative conditions are common in elderly subjects. As far as neurodegenerative diseases are concerned dementias and particularly, Alzheimer’s disease (AD) occupy a central epidemiological position given their high prevalence and their profound negative impact on the quality of life and life expectancy. The amyloid cascade hypothesis partly explains the immediate cause of AD. However, limited therapeutical success based on this hypothesis suggests more complex remote mechanisms underlying its genesis and development. For instance, the strong association of AD with another irreversible neurodegenerative pathology, without curative treatment and complex etiology such as presbycusis, reaffirms the intricate nature of the etiopathogenesis of AD. Recently, oxidative stress and frailty syndrome have been proposed, independently, as key factors underlying the onset and/or development of AD and presbycusis. Therefore, the present review summarizes recent findings about the etiology of the above-mentioned neurodegenerative diseases, providing a critical view of the possible interplay among oxidative stress, frailty syndrome, AD and presbycusis, that may help to unravel the common mechanisms shared by both pathologies. This knowledge would help to design new possible therapeutic strategies that in turn, will improve the quality of life of these patients.

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Effects of Multifunctional Antioxidants on Mitochondrial Dysfunction and Amyloid-β Metal Dyshomeostasis

Abstract: These studies demonstrate that these MFAOs have metal attenuating properties with therapeutic potential in the treatment of both AMD and AD.

Cited by 18 publications

References 44 publications

Protective Effects and Mechanisms of Dendrobium nobile Lindl. Alkaloids on PC12 Cell Damage Induced by Aβ25-35

Protective Effects and Mechanisms of Dendrobium nobile Lindl. Alkaloids on PC12 Cell Damage Induced by Aβ25-35

Antioxidants and Vasodilators for the Treatment of Noise-Induced Hearing Loss: Are They Really Effective?

Frailty Syndrome and Oxidative Stress as Possible Links Between Age-Related Hearing Loss and Alzheimer’s Disease

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