Oxidative stress as a cofactor in spinocerebellar ataxia type 2

Guevara-García, Mariela; Valle, Lizette Gil del; Velásquez-Pérez, Luis; García-Rodríguez, Julio César

doi:10.1179/1351000212y.0000000005

Cited by 18 publications

(16 citation statements)

References 47 publications

(55 reference statements)

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“…Oxidative stress has been suggested to be implicated in the pathogenesis of numerous neurodegenerative diseases, including hereditary ataxias [12]. Many studies have been conducted to validate the therapeutic roles of antioxidants in ARCAs [13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Discovery of Therapeutics Targeting Oxidative Stress in Autosomal Recessive Cerebellar Ataxia: A Systematic Review

et al. 2022

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Autosomal recessive cerebellar ataxias (ARCAs) are a heterogeneous group of rare neurodegenerative inherited disorders. The resulting motor incoordination and progressive functional disabilities lead to reduced lifespan. There is currently no cure for ARCAs, likely attributed to the lack of understanding of the multifaceted roles of antioxidant defense and the underlying mechanisms. This systematic review aims to evaluate the extant literature on the current developments of therapeutic strategies that target oxidative stress for the management of ARCAs. We searched PubMed, Web of Science, and Science Direct Scopus for relevant peer-reviewed articles published from 1 January 2016 onwards. A total of 28 preclinical studies fulfilled the eligibility criteria for inclusion in this systematic review. We first evaluated the altered cellular processes, abnormal signaling cascades, and disrupted protein quality control underlying the pathogenesis of ARCA. We then examined the current potential therapeutic strategies for ARCAs, including aromatic, organic and pharmacological compounds, gene therapy, natural products, and nanotechnology, as well as their associated antioxidant pathways and modes of action. We then discussed their potential as antioxidant therapeutics for ARCAs, with the long-term view toward their possible translation to clinical practice. In conclusion, our current understanding is that these antioxidant therapies show promise in improving or halting the progression of ARCAs. Tailoring the therapies to specific disease stages could greatly facilitate the management of ARCAs.

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Section: Introductionmentioning

confidence: 99%

Discovery of Therapeutics Targeting Oxidative Stress in Autosomal Recessive Cerebellar Ataxia: A Systematic Review

et al. 2022

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“…This emphasizes the importance of DUB activity during the recovery from oxidative stress, particularly as redox regulation of the DUBs themselves can therefore determine the duration of stress granule retention, depending on the speed of DUB oxidation reversal. Furthermore, both stress granule formation and oxidative stress have been implicated in neurological disorders such as amyotrophic lateral sclerosis and spinocerebellar ataxia type 2, and DUBs could therefore be a common element between both of these factors ( 25 , 222 , 223 , 224 , 225 ).…”

Section: Cellular Consequences Of Redox Regulation Of Dubsmentioning

confidence: 99%

Deubiquitinating enzymes (DUBs): Regulation, homeostasis, and oxidative stress response

Snyder

Silva

2021

Journal of Biological Chemistry

134

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Ubiquitin signaling is a conserved, widespread, and dynamic process in which protein substrates are rapidly modified by ubiquitin to impact protein activity, localization, or stability. To regulate this process, deubiquitinating enzymes (DUBs) counter the signal induced by ubiquitin conjugases and ligases by removing ubiquitin from these substrates. Many DUBs selectively regulate physiological pathways employing conserved mechanisms of ubiquitin bond cleavage. DUB activity is highly regulated in dynamic environments through protein–protein interaction, posttranslational modification, and relocalization. The largest family of DUBs, cysteine proteases, are also sensitive to regulation by oxidative stress, as reactive oxygen species (ROS) directly modify the catalytic cysteine required for their enzymatic activity. Current research has implicated DUB activity in human diseases, including various cancers and neurodegenerative disorders. Due to their selectivity and functional roles, DUBs have become important targets for therapeutic development to treat these conditions. This review will discuss the main classes of DUBs and their regulatory mechanisms with a particular focus on DUB redox regulation and its physiological impact during oxidative stress.

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“…It was reported in the literature that the developing cerebellum is highly vulnerable to the damaging effects of the reacting oxygen species, and the structural changes in the PCs, their dendrites, granule cells, astrocytes, microglia, neuronal axons, and oligodendroglia are observed in the induced oxidative stress [57]. The cerebellar oxidative stress-related alterations typical for SCA2 patients can be related to the altered homeostasis of the different elements in the serum or blood samples [58,59]. Thus, it was reported that the levels of copper, manganese, zinc, and vanadium are disturbed in the blood of SCA2 patients [58].…”

Section: Molecular Changes Underlying the Pc Lossmentioning

confidence: 99%

Molecular Mechanisms and Therapeutics for Spinocerebellar Ataxia Type 2

Egorova

Bezprozvanny

2019

Neurotherapeutics

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The effective therapeutic treatment and the disease-modifying therapy for spinocerebellar ataxia type 2 (SCA2) (a progressive hereditary disease caused by an expansion of polyglutamine in the ataxin-2 protein) is not available yet. At present, only symptomatic treatment and methods of palliative care are prescribed to the patients. Many attempts were made to study the physiological, molecular, and biochemical changes in SCA2 patients and in a variety of the model systems to find new therapeutic targets for SCA2 treatment. A better understanding of the uncovered molecular mechanisms of the disease allowed the scientific community to develop strategies of potential therapy and helped to create some promising therapeutic approaches for SCA2 treatment. Recent progress in this field will be discussed in this review article.

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Oxidative stress as a cofactor in spinocerebellar ataxia type 2

Cited by 18 publications

References 47 publications

Discovery of Therapeutics Targeting Oxidative Stress in Autosomal Recessive Cerebellar Ataxia: A Systematic Review

Discovery of Therapeutics Targeting Oxidative Stress in Autosomal Recessive Cerebellar Ataxia: A Systematic Review

Deubiquitinating enzymes (DUBs): Regulation, homeostasis, and oxidative stress response

Molecular Mechanisms and Therapeutics for Spinocerebellar Ataxia Type 2

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