<scp>DNA</scp> repair in trinucleotide repeat ataxias

Yau, Wai Yan; O’Connor, Emer; Sullivan, Roisin; Akijian, Layan; Wood, Nicholas W.

doi:10.1111/febs.14644

Cited by 12 publications

(15 citation statements)

References 149 publications

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“…The disturbances in DNA reparation in the adult brain are associated with the processes of aging and neurodegeneration. Oxidative metabolism is very important for neuronal functioning, but oxidative stress can cause the single-strand breaks in DNA, leading to alterations in gene expression and even cell death [16]. Cerebellar PCs have been reported to be highly affected by oxidative stress [224].…”

Section: Modifiers Of Transcription Translation and Dna Repairmentioning

confidence: 99%

“…Studies with these model systems revealed the disturbances in the morphology, biochemistry, and neurophysiology of the PCs and the cerebellar circuits [7,8] and helped to identify the possible molecular mechanisms of the disease. Aggregation, oxidative stress, disturbed cell signaling, dysregulation of calcium homeostasis, abnormal autophagy, and impaired DNA processing all seem to be involved in SCA2 molecular pathogenesis [9][10][11][12][13][14][15][16]. The promising data obtained in these studies gave rise to some perspective therapeutic approaches that may give decisive results in the treatment of SCA2 patients.…”

Section: Introductionmentioning

confidence: 98%

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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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Section: Modifiers Of Transcription Translation and Dna Repairmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Molecular Mechanisms and Therapeutics for Spinocerebellar Ataxia Type 2

Egorova

Bezprozvanny

2019

Neurotherapeutics

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“…The review is primarily intended for neurobiologists, physicians and others working in the field, or those interested in the general topic, but who are unfamiliar with DNA repair. For additional analysis, the reader is directed to other recent review articles [1][2][3][4][5][6][7][8].…”

mentioning

confidence: 99%

New developments in Huntington’s disease and other triplet repeat diseases: DNA repair turns to the dark side

Lahue

2020

Neuronal Signaling

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Huntington’s disease (HD) is a fatal, inherited neurodegenerative disease that causes neuronal death, particularly in medium spiny neurons. HD leads to serious and progressive motor, cognitive and psychiatric symptoms. Its genetic basis is an expansion of the CAG triplet repeat in the HTT gene, leading to extra glutamines in the huntingtin protein. HD is one of nine genetic diseases in this polyglutamine category, that also includes a number of inherited spinocerebellar ataxias (SCAs). Traditionally it has been assumed that HD age of onset and disease progression were solely the outcome of age-dependent exposure of neurons to toxic effects of the inherited mutant huntingtin protein. However, recent genome wide association studies have revealed significant effects of genetic variants outside of HTT. Surprisingly, these variants turn out to be mostly in genes encoding DNA repair factors, suggesting that at least some disease modulation occurs at the level of the HTT DNA itself. These DNA repair proteins are known from model systems to promote ongoing somatic CAG repeat expansions in tissues affected by HD. Thus, for triplet repeats, some DNA repair proteins seem to abandon their normal genoprotective roles and, instead, drive expansions and accelerate disease. One attractive hypothesis—still to be proven rigorously—is that somatic HTT expansions augments the disease burden of the inherited allele. If so, therapeutic approaches that lower levels of huntingtin protein may need blending with additional therapies that reduce levels of somatic CAG repeat expansions to achieve maximal effect.

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“…The authors highlight the role of epigenetics and other genetic factors as modifiers in cerebellar ataxias due to trinucleotide repeat expansions [14]. The authors highlight the role of epigenetics and other genetic factors as modifiers in cerebellar ataxias due to trinucleotide repeat expansions [14].…”

mentioning

confidence: 99%

“…Finally, Wai Yan Yau et al review the importance of DNA repair pathways in modifying inherited cerebellar ataxias. The authors highlight the role of epigenetics and other genetic factors as modifiers in cerebellar ataxias due to trinucleotide repeat expansions [14].…”

mentioning

confidence: 99%

Different faces of neurodegeneration

Abramov¹

2018

The FEBS Journal

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This Special Issue comprises nine reviews offering perspectives from the development of neurodegeneration in different pathologies to neuronal protection, providing new views on the mechanism of neurodegeneration and associated processes and a summary of the progress in neuroscience. We hope you find these reviews interesting and informative and we thank the authors for these excellent contributions to The FEBS Journal.

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DNA repair in trinucleotide repeat ataxias

Cited by 12 publications

References 149 publications

Molecular Mechanisms and Therapeutics for Spinocerebellar Ataxia Type 2

Molecular Mechanisms and Therapeutics for Spinocerebellar Ataxia Type 2

New developments in Huntington’s disease and other triplet repeat diseases: DNA repair turns to the dark side

Different faces of neurodegeneration

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