Superoxide dismutase and free radicals in sporadic amyotrophic lateral sclerosis: relationship to clinical data

Ihara, Yoshito; Mori, Akitane; Hayabara, Toshiyuki; Kawai, Motoko; Namba, Reiko; Nobukuni, Keigo; Satô, Keiko; Kibata, Masayoshi

doi:10.1016/0022-510x(95)00193-6

Cited by 20 publications

(10 citation statements)

References 8 publications

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“…Oxidative damage to spinal cord proteins [1][2][3] , presence of 4-hydroxynonenal, a lipid peroxidation product, in CSF [4] and increased 3-nitrotyrosine (NT) in CSF [5] were observed in ALS patients, even if not all previous studies are in agreement [6] . Moreover, significantly higher levels of 4-hydroxynonenal in serum [7] , increased levels of free 8-hydroxydeoxyguanosine (a marker of DNA damage) in urine, plasma and CSF [8] , high levels of blood free radicals [9] , thiobarbituric-acid-reactive species, protein-associated carbonyls [10,11] and increased total protein oxidation in lymphocytes [12] have also been reported in ALS patients.…”

Section: Introductionmentioning

confidence: 99%

Lack of Evidence for Oxidative Stress in Sporadic Amyotrophic Lateral Sclerosis Fibroblasts

et al. 2008

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Background: It is conceivable that an early therapeutic intervention in amyotrophic lateral sclerosis (ALS) would lead to better results in terms of disease progression for these patients. One possible strategy to increase the sensitivity of the diagnosis is represented by the use of biological parameters reflecting, for example, oxidative stress alterations associated with ALS. Such biomarkers would be valuable tools both for a better diagnostic evaluation and for studying the impact of therapeutic interventions on the disease course. A special category of experimental models is represented by peripheral cells obtained directly from patients (ex vivo). Objective: In this study, primary fibroblasts obtained from 10 sporadic ALS (SALS) patients and 10 healthy matched controls were used to investigate a panel of parameters related to the oxidative status. Methods: Reactive oxygen species production, protein carbonylation and nitration, susceptibility to hydrogen peroxide exposure, p38-mitogen-activated protein kinase activation and adenosine triphosphate intracellular content were evaluated. Results: No significant difference was observed in all investigated parameters between patient and control cells, and no correlation with the disease severity was found. Conclusion: Collectively, our data show no major alterations of the oxidative and bioenergetic status in SALS cultured fibroblasts, suggesting that these cells do not represent a useful model to study the oxidative dysfunction associated with SALS.

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Section: Introductionmentioning

confidence: 99%

Lack of Evidence for Oxidative Stress in Sporadic Amyotrophic Lateral Sclerosis Fibroblasts

et al. 2008

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“…The presence of aberrant or persistent stress granules is also associated with the cellular pathology of age-related diseases, neurodegeneration and some cancers (Mateju et al, 2017; Protter and Parker, 2016; Turakhiya et al, 2018). Furthermore, increased basal stress levels and defects in cellular stress responses have been suggested to occur in DM1 (Huichalaf et al, 2010; Ihara et al, 1995; Kumar et al, 2014; Toscano et al, 2005; Usuki and Ishiura, 1998; Usuki et al, 2000). Here we report delayed stress granule formation and premature stress granule loss in cell culture models of DM1, together with altered biophysical characteristics of the closely related P-bodies.…”

Section: Discussionmentioning

confidence: 99%

“…Increased cellular stress, resulting from the presence of CUGexp RNA foci has been suggested as a pathological effector in DM1 (Huichalaf et al, 2010; Ihara et al, 1995; Kumar et al, 2014; Toscano et al, 2005; Usuki and Ishiura, 1998; Usuki et al, 2000). Both MBNL1 and CUGBP1, key proteins implicated in the pathology of DM1, have been identified in stress granules in mammalian cells (Fujimura et al, 2008; Onishi et al, 2008), and increased incidence of stress granules reported in DM1 myoblasts compared to controls under normal growth conditions (Huichalaf et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Phase-separated stress granules and processing bodies are compromised in Myotonic Dystrophy Type 1

Gulyurtlu

Magon

Guest

et al. 2021

Preprint

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RNA regulation in mammalian cells requires complex physical compartmentalisation using structures thought to be formed by liquid-liquid phase separation. Disruption of these structures is implicated in numerous degenerative diseases. Myotonic Dystrophy Type 1 (DM1) is a multi-systemic trinucleotide repeat disorder resulting from a CTG expansion in the dystonia myotonica protein kinase gene (DMPK). The cellular hall-mark of DM1 is the formation of nuclear foci containing expanded DMPK RNA (CUGexp). We report here the deregulation of stress granules and processing bodies (P-bodies), two cytoplasmic structures key for mRNA regulation, in cell culture models of DM1. Alterations to the rates of formation and dispersal of stress granules suggest an altered ability to respond to stress associated with DM1, while changes to the structure and dynamics of stress granules and P- bodies suggest that a more widespread alteration to the biophysical properties of cellular structures may be a consequence of the presence of CUGexp RNA.

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“…Regarding the antioxidant enzyme activity of SOD, several studies have shown that SOD activity is elevated in red blood cells (RBC) and plasma from sporadic ALS patients [167,171,172], whereas it has been shown that the activity is not changed significantly in RBC and plasma from sporadic ALS patients and reduced in RBC and CSF from sporadic and familial ALS patients [165,166,168,[173][174][175][176][177]. Intriguingly, it has been reported that the antioxidant enzyme activity of SOD in bulbar onset sporadic ALS was significantly higher than in spinal onset sporadic ALS [167].…”

Section: Proteinmentioning

confidence: 99%

Biomolecular Modifications Linked to Oxidative Stress in Amyotrophic Lateral Sclerosis: Determining Promising Biomarkers Related to Oxidative Stress

2021

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Reduction–oxidation reactions are essential to cellular homeostasis. Oxidative stress transcends physiological antioxidative system damage to biomolecules, including nucleic acids and proteins, and modifies their structures. Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease. The cells present in the central nervous system, including motor neurons, are vulnerable to oxidative stress. Neurodegeneration has been demonstrated to be caused by oxidative biomolecular modifications. Oxidative stress has been suggested to be involved in the pathogenesis of ALS. Recent progress in research on the underlying mechanisms of oxidative stress in ALS has led to the development of disease-modifying therapies, including edaravone. However, the clinical effects of edaravone remain limited, and ALS is a heretofore incurable disease. The reason for the lack of reliable biomarkers and the precise underlying mechanisms between oxidative stress and ALS remain unclear. As extracellular proteins and RNAs present in body fluids and represent intracellular pathological neurodegenerative processes, extracellular proteins and/or RNAs are predicted to promise diagnosis, prediction of disease course, and therapeutic biomarkers for ALS. Therefore, we aimed to elucidate the underlying mechanisms between oxidative stress and ALS, and promising biomarkers indicating the mechanism to determine whether therapy targeting oxidative stress can be fundamental for ALS.

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Superoxide dismutase and free radicals in sporadic amyotrophic lateral sclerosis: relationship to clinical data

Cited by 20 publications

References 8 publications

Lack of Evidence for Oxidative Stress in Sporadic Amyotrophic Lateral Sclerosis Fibroblasts

Lack of Evidence for Oxidative Stress in Sporadic Amyotrophic Lateral Sclerosis Fibroblasts

Phase-separated stress granules and processing bodies are compromised in Myotonic Dystrophy Type 1

Biomolecular Modifications Linked to Oxidative Stress in Amyotrophic Lateral Sclerosis: Determining Promising Biomarkers Related to Oxidative Stress

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