Zewen Liu, Zhangpin Ren, Jun Zhang, Chia-Chen Chuang, Eswar Kandaswamy, Tingyang Zhou, and Li Zuo; Front Physiol. 2018; 9: 477. doi:10.3389/fphys.2018.00477
The combination of vitamin E and coenzyme Q10 improves energy generation in some cases of Friedreich ataxia by attenuating OS and restoring mitochondrial function. Numerous studies have been performed to investigate the therapeutic effects of natural antioxidants on neurodegenerative disorders; however, mixed results have been yielded.
Saturday, June 9, 2018
RNA Editing and Retrotransposons in Neurology
Heinz Krestel and Jochen C. Meier; Front Mol Neurosci. 2018; 11: 163. doi:10.3389/fnmol.2018.00163
Friedreich ataxia is the best known and most commonly inherited form of spinocerebellar ataxia. It can be caused by mutations or, in 98% of cases, by GAA trinucleotide-repeat expansions located at the center of an AluSq element in intron 1 of the frataxin (FXN) gene. Friedreich ataxia is the only known disease caused by abnormal expansion of a GAA trinucleotide-repeat sequence. It was suggested that GAA repeats arose by mutation or A-to-G conversion from poly(A) tracts of Alu elements. Many longer GAA repeats in the human genome can be found in the 3′ poly(A) tracts of Alu elements, but it was suggested that A-to-G conversion that led to poly-GAA repeats in Friedreich ataxia arose in the central linker region of Alu elements. Beyond GAA repeats, Alu elements were in general described to be a source for microsatellites. Expansion of trinucleotide repeats was proposed to have arisen in Friedreich ataxia rather by in-tandem duplication up to a certain repeat length. From a certain repeat length onwards, genetic instability was proposed to contribute to additional repeat expansion, which is known in Neurology as anticipation. GAA repeat expansions affect pre-mRNA processing by inducing the accumulation of upstream splicing intermediates. No interaction of RNA editing with these genetic rearrangements in Friedreich ataxia has been reported.
Friedreich ataxia is the best known and most commonly inherited form of spinocerebellar ataxia. It can be caused by mutations or, in 98% of cases, by GAA trinucleotide-repeat expansions located at the center of an AluSq element in intron 1 of the frataxin (FXN) gene. Friedreich ataxia is the only known disease caused by abnormal expansion of a GAA trinucleotide-repeat sequence. It was suggested that GAA repeats arose by mutation or A-to-G conversion from poly(A) tracts of Alu elements. Many longer GAA repeats in the human genome can be found in the 3′ poly(A) tracts of Alu elements, but it was suggested that A-to-G conversion that led to poly-GAA repeats in Friedreich ataxia arose in the central linker region of Alu elements. Beyond GAA repeats, Alu elements were in general described to be a source for microsatellites. Expansion of trinucleotide repeats was proposed to have arisen in Friedreich ataxia rather by in-tandem duplication up to a certain repeat length. From a certain repeat length onwards, genetic instability was proposed to contribute to additional repeat expansion, which is known in Neurology as anticipation. GAA repeat expansions affect pre-mRNA processing by inducing the accumulation of upstream splicing intermediates. No interaction of RNA editing with these genetic rearrangements in Friedreich ataxia has been reported.
Epigenetic Regulation in Neurodegenerative Diseases
Amit Berson, Raffaella Nativio, Shelley L. Berger, Nancy M. Bonini, Trends in Neurosciences, Available online 7 June 2018, ISSN 0166-2236, doi:10.1016/j.tins.2018.05.005.
Mechanisms of epigenetic regulation, including DNA methylation, chromatin remodeling, and histone post-translational modifications, are involved in multiple aspects of neuronal function and development. Recent discoveries have shed light on critical functions of chromatin in the aging brain, with an emerging realization that the maintenance of a healthy brain relies heavily on epigenetic mechanisms. Here, we present recent advances, with a focus on histone modifications and the implications for several neurodegenerative diseases including Alzheimer’s disease (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). We highlight common and unique epigenetic mechanisms among these situations and point to emerging therapeutic approaches.
Mechanisms of epigenetic regulation, including DNA methylation, chromatin remodeling, and histone post-translational modifications, are involved in multiple aspects of neuronal function and development. Recent discoveries have shed light on critical functions of chromatin in the aging brain, with an emerging realization that the maintenance of a healthy brain relies heavily on epigenetic mechanisms. Here, we present recent advances, with a focus on histone modifications and the implications for several neurodegenerative diseases including Alzheimer’s disease (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). We highlight common and unique epigenetic mechanisms among these situations and point to emerging therapeutic approaches.
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