Oxidative stress in neurodegeneration in dentatorubral-pallidoluysian atrophy

Miyata, Rie; Hayashi, Masaharu; Tanuma, Naoyuki; Shioda, Kei; Fukatsu, Ryou; Mizutani, Shuki

doi:10.1016/j.jns.2007.08.025

Cited by 23 publications

(11 citation statements)

References 29 publications

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“…Oxidative stress originates from an imbalance between the production of reactive oxygen species and reactive nitrogen species and the antioxidant capacities of cells and organs [ 3 ]. Oxidative stress has been confirmed to play a role in adult-onset neurodegenerative diseases, such as Alzheimer's disease [ 4 ], and we confirmed the involvement of oxidative neuronal damage in child-onset and adult neurodegenerative diseases, such as dentatorubral-pallidoluysian atrophy and superficial siderosis [ 5 , 6 ]. We clarified the accumulation of oxidative stress markers in the basal ganglia in autopsy rains in XPA and Cockayne syndrome (CS), having a genetic defect in transcription-coupled repair, which results in multiple organ impairment and various neurological disorders [ 7 ].…”

Section: Introductionsupporting

confidence: 76%

Circadian Rhythms of Oxidative Stress Markers and Melatonin Metabolite in Patients with Xeroderma Pigmentosum Group A

Miyata

Tanuma

Sakuma

et al. 2016

Oxidative Medicine and Cellular Longevity

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Xeroderma pigmentosum group A (XPA) is a genetic disorder in DNA nucleotide excision repair (NER) with severe neurological disorders, in which oxidative stress and disturbed melatonin metabolism may be involved. Herein we confirmed the diurnal variation of melatonin metabolites, oxidative stress markers, and antioxidant power in urine of patients with XPA and age-matched controls, using enzyme-linked immunosorbent assay (ELISA). The peak of 6-sulfatoxymelatonin, a metabolite of melatonin, was seen at 6:00 in both the XPA patients and controls, though the peak value is lower, specifically in the younger age group of XPA patients. The older XPA patients demonstrated an increase in the urinary levels of 8-hydroxy-2′-deoxyguanosine and hexanoyl-lysine, a marker of oxidative DNA damage and lipid peroxidation, having a robust peak at 6:00 and 18:00, respectively. In addition, the urinary level of total antioxidant power was decreased in the older XPA patients. Recently, it is speculated that oxidative stress and antioxidant properties may have a diurnal variation, and the circadian rhythm is likely to influence the NER itself. We believe that the administration of melatonin has the possibility of ameliorating the augmented oxidative stress in neurodegeneration, especially in the older XPA patients, modulating the melatonin metabolism and the circadian rhythm.

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Section: Introductionsupporting

confidence: 76%

Circadian Rhythms of Oxidative Stress Markers and Melatonin Metabolite in Patients with Xeroderma Pigmentosum Group A

Miyata

Tanuma

Sakuma

et al. 2016

Oxidative Medicine and Cellular Longevity

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“…It has been suggested that in polyQ disorders increasing oxidative stress and inability to protect against free radicals with age could lead to mitochondrial dysfunction and cell damage [120–123]. In accordance with this, a cell model overexpressing mutant ataxin-3 with 78 CAGs showed reduced antioxidant enzyme levels, increased mitochondrial DNA damage, and reduced energy supply, which indicates impaired mitochondrial function [124].…”

Section: Mitochondrial Dysfunction In Sca3mentioning

confidence: 91%

Ataxin-3 Protein and RNA Toxicity in Spinocerebellar Ataxia Type 3: Current Insights and Emerging Therapeutic Strategies

2013

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Ataxin-3 is a ubiquitously expressed deubiqutinating enzyme with important functions in the proteasomal protein degradation pathway and regulation of transcription. The C-terminus of the ataxin-3 protein contains a polyglutamine (PolyQ) region that, when mutationally expanded to over 52 glutamines, causes the neurodegenerative disease spinocerebellar ataxia 3 (SCA3). In spite of extensive research, the molecular mechanisms underlying the cellular toxicity resulting from mutant ataxin-3 remain elusive and no preventive treatment is currently available. It has become clear over the last decade that the hallmark intracellular ataxin-3 aggregates are likely not the main toxic entity in SCA3. Instead, the soluble PolyQ containing fragments arising from proteolytic cleavage of ataxin-3 by caspases and calpains are now regarded to be of greater influence in pathogenesis. In addition, recent evidence suggests potential involvement of a RNA toxicity component in SCA3 and other PolyQ expansion disorders, increasing the pathogenic complexity. Herein, we review the functioning of ataxin-3 and the involvement of known protein and RNA toxicity mechanisms of mutant ataxin-3 that have been discovered, as well as future opportunities for therapeutic intervention.

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“…For example, Huntington's disease is caused by polyQ (more than 35 repeats) in the Huntington protein that results in neuronal cell death (23). In addition, aberrant expression of superoxide dismutase and accumulation of oxidative products were also observed in a CAG-repeat disease (24).…”

Section: Discussionmentioning

confidence: 99%

An elongated tract of polyQ in the carboxyl‑terminus of human α1A calcium channel induces cell apoptosis by nuclear translocation

Sun

et al. 2020

Oncol Rep

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An aberrant elongated tract of glutamine residues (polyQ) in proteins induces multiple diseases treated in the clinic. In our previous study of progressive myoclonic epilepsy (PME), using whole-exome sequencing, a mutant Cav2.1 protein with an aberrant elongated polyQ tract was identified in PME patients. To investigate the molecular mechanism and cell biology of this aberrant elongated polyQ tract, wild-type Cav2.1 with 13 polyQ repeats (Cav2.1 wt-Q13) and mutant-type Cav2.1 with 26 polyQ repeats (Cav2.1 mt-Q26) were prepared and introduced into human SH-SY5Y neuroblastoma cells. Using a WST-1 assay, it was revealed that Cav2.1 mt-Q26 markedly suppressed the proliferation of the SH-SY5Y cells, a result not observed for the Cav2.1 wt-Q13-transfected cells. It was also revealed that Cav2.1 mt and its truncated molecules suppressed cell proliferation by inducing apoptosis rather than arresting the cell cycle. Further investigations indicated a nuclear translocation phenomenon associated with the Cav2.1 mt molecules. Mechanistically, it was revealed that the Cav2.1 mt molecules activated the Bcl-2/Bax, caspase-3 and poly ADP-ribose polymerase (PARP) apoptotic pathways. The present study may provide new insights for interpreting the pathogenesis of PME and the relationship among polyQ, CACNA1A gene mutations and PME.

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Oxidative stress in neurodegeneration in dentatorubral-pallidoluysian atrophy

Cited by 23 publications

References 29 publications

Circadian Rhythms of Oxidative Stress Markers and Melatonin Metabolite in Patients with Xeroderma Pigmentosum Group A

Circadian Rhythms of Oxidative Stress Markers and Melatonin Metabolite in Patients with Xeroderma Pigmentosum Group A

Ataxin-3 Protein and RNA Toxicity in Spinocerebellar Ataxia Type 3: Current Insights and Emerging Therapeutic Strategies

An elongated tract of polyQ in the carboxyl‑terminus of human α1A calcium channel induces cell apoptosis by nuclear translocation

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