明星八卦

Our project investigates the effectiveness of different antioxidants in treating Friedreich’s ataxia (FRDA) by targeting the Nrf2 pathway to reduce oxidative stress and improve cellular function.

Friedreich’s ataxia (FRDA) is a serious genetic disorder that damages the nervous system over time. This leads to problems like difficulty walking, loss of sensation in the limbs, and trouble speaking.

The disease often causes severe disability, heart failure, and early death, having a profound effect on individuals and families.

Our project looks at how effective different antioxidants are in reducing the harmful effects of FRDA. The research uses cell cultures and mouse models to study these effects, focusing on the Nrf2 pathway. Nrf2 is a protein that helps protect cells from damage caused by oxidative stress.

Understanding Friedreich’s ataxia

FRDA is an inherited neurodegenerative disorder caused by the epigenetic silencing of the frataxin gene. It's the most common inherited ataxia, affecting 1 in 50,000 Caucasians, and is characterised by neurodegeneration, cardiomyopathy, diabetes mellitus, and skeletal deformities.

There is currently no effective treatment for FRDA. Although recent clinical trials have investigated potential therapies, none have significantly improved the neurological symptoms associated with FRDA. We urgently need more effective treatments.

FRDA results in increased oxidative stress and mitochondrial dysfunction, which drive disease progression.

Studies have shown that frataxin deficiency inhibits Nrf2, impairing antioxidant defences and leading to increased lipid peroxidation.

Many experimental approaches have been explored to activate the Nrf2 pathway and prevent lipid peroxidation. We aim to investigate the molecular mechanisms of FRDA to develop new therapeutic strategies for its diagnosis and treatment.

Our project focuses on the therapeutic efficacy of different antioxidants to reduce the molecular and biochemical effects of FRDA using cell culture and mouse models.

Targeting the Nrf2 pathway in FRDA treatment

The main goal of this research is to see how well antioxidants that activate the Nrf2 pathway work as treatments for FRDA.

Oxidative stress and mitochondrial problems are key issues in FRDA. By targeting the Nrf2 pathway, we hope to find new ways to ease symptoms and slow down the disease.

Our project’s unique focus on Nrf2 activation as a therapeutic strategy for FRDA sets it apart from existing research in the field. Our research also uses both cell cultures and mouse models, giving a detailed look at how antioxidants affect FRDA.

By using various experimental techniques, we can get a deeper understanding of how these antioxidants work, which could lead to new, targeted treatments.

Implications for neurodegenerative disease treatment

FRDA has a huge impact on people and their families, leading to severe disability, heart failure, and early death. Although FRDA is rare, the insights from this study could help with other neurodegenerative diseases like Alzheimer's, Parkinson's, and Huntington's, which have similar underlying problems. Understanding how antioxidants or other treatments can change disease pathways could open up new ways to treat these conditions.

By focusing on the Nrf2 pathway, this research aims to tackle the oxidative stress and mitochondrial dysfunction at the heart of FRDA. The findings could greatly improve the quality of life for those with FRDA and offer new treatment options for other neurodegenerative diseases.

Publications

Edzeamey, F. J., Ramchunder, Z., Pourzand, C., and Anjomani-Virmouni, S. (2024). Emerging antioxidant therapies in Friedreich's ataxia. Frontiers in Pharmacology, 15, 1-17. ISSN: 1663-9812.

Anjomani-Virmouni, S., et al. (2015). A novel GAA-repeat-expansion-based mouse model of Friedreich's ataxia. Disease Models & Mechanisms, 8(3), 225-235.

Paupe, V., et al. (2009). Impaired nuclear Nrf2 translocation undermines the oxidative stress response in Friedreich ataxia. PLoS One, 4(1), e4253.

D'Oria, V., et al. (2013). Frataxin deficiency leads to reduced expression and impaired translocation of NF-E2-related factor (Nrf2) in cultured motor neurons. International Journal of Molecular Sciences, 14(4), 7853-7865.

Shan, Y., et al. (2013). Frataxin deficiency leads to defects in expression of antioxidants and Nrf2 expression in dorsal root ganglia of the Friedreich's ataxia YG8R mouse model. Antioxidants & Redox Signaling, 19(13), 1481-1493.