The role of oxidative stress in neurodegenerative diseases and potential antioxidant therapies

Bailo, P; Martín, Elena; Calmarza, Pilar; Breva, Silvia Montolio; Gómez, Adrián Bravo; Giráldez, Adela Pozo; Callau, Joan José Sánchez-Pascuala; Santamaría, Juana Maria Vaquer; Khialani, Anita Dayaldasani; Micó, Concepción Cerdá; Andreu, Jordi Camps; Tormo, Guillermo Sáez; Gallifa, Isabel Fort

doi:10.1515/almed-2022-0111

Cited by 12 publications

(10 citation statements)

References 45 publications

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“…These results can be interpreted in the context of the established role of OS in neuronal damage [27][28][29]. For instance, the association of GST, a key enzyme in detoxifying reactive oxygen species, suggests that individuals with certain genetic variants may have a reduced capacity to mitigate OS, thereby increasing their risk of PDPN [30,31].…”

Section: Discussionmentioning

confidence: 94%

The influence of genetic predisposition to oxidative stress on painful diabetic peripheral neuropathy: A Mendelian randomization study

Liyan Zou,

Duosheng Zhu,

Min Gong

et al. 2024

Cell Mol Biol (Noisy-le-grand)

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Genetic predisposition to oxidative stress (OS) may influence the risk of Painful Diabetic Peripheral Neuropathy (PDPN). This study employed a Mendelian Randomization (MR) approach to investigate the causal relationship between genetic predisposition to OS and PDPN. Genetic instruments associated with OS biomarkers were selected as exposures. Summary-level data on PDPN was obtained from the largest available genomewide association study (GWAS). MR analyses were conducted using the inverse-variance weighted (IVW) method, with sensitivity analyses employing the MR-Egger, weighted median, and MR-PRESSO approaches. Genetic predisposition to increased glutathione S-transferase (GST) activity was associated with a reduced risk of PDPN (OR=0.66, 95%CI: 0.49-0.89, P=0.006). Higher ascorbate levels conferred a protective effect against PDPN (OR=0.83, 95%CI: 0.71-0.97, P=0.018). No significant association was observed between genetic predisposition to OS biomarkers and PDPN severity. Genetic predisposition to increased GST activity and higher ascorbate levels protect against the development of PDPN, suggesting a causal relationship.

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Section: Discussionmentioning

confidence: 94%

The influence of genetic predisposition to oxidative stress on painful diabetic peripheral neuropathy: A Mendelian randomization study

Liyan Zou,

Duosheng Zhu,

Min Gong

et al. 2024

Cell Mol Biol (Noisy-le-grand)

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“…Protection against oxidative stress is dependent on endogenous antioxidants, including GSH, SOD, GPx, and CAT. However, neurons have been demonstrated to exhibit a weaker antioxidant defense and limited regenerative capacity relative to other tissue cells [43].…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV Reduces Mutant Ataxin-3 Levels and Supports Mitochondrial Function in Spinocerebellar Ataxia Type 3

Lin,

Cheng,

Chang

et al. 2023

Preprint

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This study investigated the effects of astragaloside IV (AST) on the neurodegenerative disease of spinocerebellar ataxia type 3 (SCA3). Human neuroblastoma SK-N-SH cells expressing mutant ataxin-3 protein with 78 CAG repeats (MJD78) were used as an in vitro model, and SCA3 transgenic mice harboring an allele with a pathological polyglutamine tract with expanded 84 CAG repeats (SCA3 84Q) were used as an in vivo model. Protein expression analysis revealed that AST treatment reduced mutant ataxin-3 protein expression and aggregation via increased the autophagic flux in the MJD78 cells. Oxidative stress levels were elevated in the MJD78 cells but were reduced after AST treatment, which also increased antioxidant capacity; these findings were obtained using flow cytometry and antioxidant enzyme activity assay. Furthermore, treatment with AST ameliorated mitochondrial dysfunction in the MJD78 cells, including that related to mitochondrial membrane potential, respiration, and mitochondrial dynamics. Additionally, AST administration improved motor function and provided protection against Purkinje cell loss in the cerebellum of the SCA3 84Q mice. In conclusion, AST administration increase the capability of antioxidants and reduced either cellular or mitochondrial oxidative stress and improve the process of mitochondrial quality control by fusion, fission, and autophagy. Summarizing, aforementioned mechanisms reduced intracellular mutant ataxin-3 protein aggregation to achieve therapeutic effectiveness in the SCA3 model.

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“…A further point is that the brain and CNS tissue have a high content of lipids, which can obviously be subjected to the peroxidation induced by ROS, and metals. Finally, the low antioxidant defense of neurons and their reduced regenerative capacity should be considered to fully understand the high susceptibility of this tissue to OS damage [10].…”

Section: Introductionmentioning

confidence: 99%

Saffron the “Red Gold” and Its CNS Activity: A Challenge for Future Applications in Nutraceuticals

Sut,

Gherardi,

Ruzza

et al. 2024

Journal of Food Biochemistry

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Saffron, indicated as “the red gold,” is an extraordinary spice with a unique aroma and organoleptic properties that is largely diffused in food preparation as well as a traditional medicine in many countries of the world. In the last years, several studies have considered this spice for CNS-based disorders showing its potential usefulness. In this review, we considered the role of saffron as a nutraceutical for the management of the most diffused CNS diseases considering the important role of oxidative stress on the pathogenesis of such diseases. In fact, recent findings support a crucial role of oxidative stress in different CNS diseases suggesting an important role of antioxidants. Preclinical and clinical evidence of its efficacy in different physiopathological pathways involved in several CNS diseases were discussed showing evidence of pharmacological activities and beneficial effects in pathological models or in small trials. Due to low toxicity and significant activities on oxidative stress and inflammation as well as the ability to modulate mitochondrial function, the saffron extracts and their constituents appear to be promising nutraceutical active compounds in this area. Further investigations are in progress to assess the efficacy and safety of preventive agents as nutraceuticals or as adjuvant compounds to be used in combinations with other therapeutic approaches. Saffron nutraceuticals with significant antioxidant activity can be useful in improving the quality of life of patients suffering from several different pathological conditions related to CNS. In this review, we summarized the more recent studies showing that standardized saffron products can be a valuable instrument of well-being due to their effects on multiple targets that support the health of the brain and related tissues.

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The role of oxidative stress in neurodegenerative diseases and potential antioxidant therapies

Cited by 12 publications

References 45 publications

The influence of genetic predisposition to oxidative stress on painful diabetic peripheral neuropathy: A Mendelian randomization study

The influence of genetic predisposition to oxidative stress on painful diabetic peripheral neuropathy: A Mendelian randomization study

Astragaloside IV Reduces Mutant Ataxin-3 Levels and Supports Mitochondrial Function in Spinocerebellar Ataxia Type 3

Saffron the “Red Gold” and Its CNS Activity: A Challenge for Future Applications in Nutraceuticals

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