scholarly journals Molecular Defects in Friedreich’s Ataxia: Convergence of Oxidative Stress and Cytoskeletal Abnormalities

2020 ◽  
Vol 7 ◽  
Author(s):  
Frances M. Smith ◽  
Daniel J. Kosman
Keyword(s):  
Oxidative Stress ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Molecular Defects

scholarly journals Oxidative stress modulates rearrangement of endoplasmic reticulum-mitochondria contacts and calcium dysregulation in a Friedreich's ataxia model

Redox Biology ◽  
2020 ◽  
Vol 37 ◽  
pp. 101762
Author(s):  
Laura R. Rodríguez ◽  
Pablo Calap-Quintana ◽  
Tamara Lapeña-Luzón ◽  
Federico V. Pallardó ◽  
Stephan Schneuwly ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Calcium Dysregulation

Oxidative stress, mitochondrial dysfunction and cellular stress response in Friedreich's ataxia

2005 ◽  
Vol 233 (1-2) ◽  
pp. 145-162 ◽  
Author(s):  
Vittorio Calabrese ◽  
Raffaele Lodi ◽  
Caterina Tonon ◽  
Velia D'Agata ◽  
Maria Sapienza ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Mitochondrial Dysfunction ◽  
Cellular Stress ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Cellular Stress Response

scholarly journals Liver Growth Factor (LGF) Upregulates Frataxin Protein Expression and Reduces Oxidative Stress in Friedreich’s Ataxia Transgenic Mice

2016 ◽  
Vol 17 (12) ◽  
pp. 2066 ◽  
Author(s):  
Lucía Calatrava-Ferreras ◽  
Rafael Gonzalo-Gobernado ◽  
Diana Reimers ◽  
Antonio Herranz ◽  
María Casarejos ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Factor ◽  
Transgenic Mice ◽  
Protein Expression ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Liver Growth

Does oxidative stress contribute to the pathology of Friedreich's ataxia? A radical question

2010 ◽  
Vol 24 (7) ◽  
pp. 2152-2163 ◽  
Author(s):  
Jeffrey S. Armstrong ◽  
Omar Khdour ◽  
Sidney M. Hecht
Keyword(s):  
Oxidative Stress ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia

scholarly journals Effects of tocotrienol supplementation in Friedreich’s ataxia: A model of oxidative stress pathology

2019 ◽  
Vol 245 (3) ◽  
pp. 201-212
Author(s):  
Alessandra Bolotta ◽  
Antonella Pini ◽  
Provvidenza M Abruzzo ◽  
Alessandro Ghezzo ◽  
Alessandra Modesti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Responses ◽  
Genetic Disorder ◽  
Combined Treatment ◽  
Antioxidant Properties ◽  
Autosomal Recessive Disorder ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Suitable Model ◽  
One Year

Friedreich’s ataxia is an autosomal recessive disorder characterized by impaired mitochondrial function, resulting in oxidative stress. In this study, we aimed at evaluating whether tocotrienol, a phytonutrient that diffuses easily in tissues with saturated fatty layers, could complement the current treatment with idebenone, a quinone analogue with antioxidant properties. Five young Friedreich’s ataxia patients received a low-dose tocotrienol supplementation (5 mg/kg/day), while not discontinuing idebenone treatment. Several oxidative stress markers and biological parameters related to oxidative stress were evaluated at the time of initiation of treatment and 2 and 12 months post-treatment. Some oxidative stress-related parameters and some inflammation indices were altered in Friedreich’s ataxia patients taking idebenone alone and tended to be normal values following tocotrienol supplementation; likewise, a cardiac magnetic resonance study showed some improvement following one-year tocotrienol treatment. The pathway by which tocotrienol affects the Nrf2 modulation of hepcidin gene expression, a peptide involved in iron handling and in inflammatory responses, is viewed in the light of the disruption of the iron intracellular distribution and of the Nrf2 anergy characterizing Friedreich’s ataxia. This research provides a suitable model to analyze the efficacy of therapeutic strategies able to counteract the excess free radicals in Friedreich’s ataxia, and paves the way to long-term clinical studies. Impact statement Oxidative stress is involved in the pathogenesis of Friedreich's ataxia (FRDA), a genetic disorder causing neurodegeneration due to the dramatic reduction in the expression of frataxin. To date, no cure is available for FRDA patients. In some countries, FRDA patients assume idebenone in order to counteract the effects of frataxin deficiency. We demonstrate that idebenone treatment alone is not able to abrogate oxidative stress in FRDA patients, whereas the combined treatment with tocotrienols might be more efficient and perhaps produce clinical improvement. In fact, a decrease in oxidative stress and inflammation markers can be seen after two months and is more pronounced after one year of treatment. This is, in our opinion, valuable information for clinicians, since idebenone is the treatment of choice for FRDA patients in some countries.

scholarly journals Antioxidant Therapies and Oxidative Stress in Friedreich’s Ataxia: The Right Path or Just a Diversion?

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 664 ◽  
Author(s):  
Laura R. Rodríguez ◽  
Tamara Lapeña ◽  
Pablo Calap-Quintana ◽  
María Dolores Moltó ◽  
Pilar Gonzalez-Cabo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Clinical Trials ◽  
Autosomal Recessive ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Antioxidant Defenses ◽  
Stress Markers ◽  
The One ◽  
The Right ◽  
And Oxidative Stress

Friedreich’s ataxia is the commonest autosomal recessive ataxia among population of European descent. Despite the huge advances performed in the last decades, a cure still remains elusive. One of the most studied hallmarks of the disease is the increased production of oxidative stress markers in patients and models. This feature has been the motivation to develop treatments that aim to counteract such boost of free radicals and to enhance the production of antioxidant defenses. In this work, we present and critically review those “antioxidant” drugs that went beyond the disease’s models and were approved for its application in clinical trials. The evaluation of these trials highlights some crucial aspects of the FRDA research. On the one hand, the analysis contributes to elucidate whether oxidative stress plays a central role or whether it is only an epiphenomenon. On the other hand, it comments on some limitations in the current trials that complicate the analysis and interpretation of their outcome. We also include some suggestions that will be interesting to implement in future studies and clinical trials.

Paradoxical disruption of Nrf2 signaling despite mitochondrial iron driven oxidative stress in Friedreich’s ataxia cardiomyopathy

2018 ◽  
Vol 128 ◽  
pp. S131
Author(s):  
Michael Huang ◽  
Amy Anzovino ◽  
Shannon Chiang ◽  
Bronwyn Brown ◽  
Clare Hawkins ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Mitochondrial Iron

scholarly journals A new tool to determine the cellular metabolic landscape: nanotechnology to the study of Friedreich’s ataxia

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tommaso Vannocci ◽  
Simone Dinarelli ◽  
Marco Girasole ◽  
Annalisa Pastore ◽  
Giovanni Longo
Keyword(s):  
Oxidative Stress ◽  
Time Resolution ◽  
Metabolic Response ◽  
High Sensitivity ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Single Cell Level ◽  
Cellular Model ◽  
Cell Level ◽  
Non Invasive

AbstractUnderstanding the cell response to oxidative stress in disease is an important but difficult task. Here, we demonstrate the feasibility of using a nanomotion sensor to study the cellular metabolic landscape. This nanosensor permits the non-invasive real-time detection at the single-cell level and offers high sensitivity and time resolution. We optimised the technique to study the effects of frataxin overexpression in a cellular model of Friedreich’s ataxia, a neurodegenerative disease caused by partial silencing of the FXN gene. Previous studies had demonstrated that FXN overexpression are as toxic as silencing, thus indicating the importance of a tight regulation of the frataxin levels. We probed the effects of frataxin overexpression in the presence of oxidative stress insults and measured the metabolic response by the nanosensor. We show that the nanosensor provides new detailed information on the metabolic state of the cell as a function of time, that agrees with and complements data obtained by more traditional techniques. We propose that the nanosensor can be used in the future as a new and powerful tool to study directly how drugs modulate the effects of oxidative stress on Friedreich’s ataxia patients and, more in general, on other neurodegenerative processes.

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