Increased Oxidative Stress and Impaired Antioxidant Response in Lafora Disease

@article{RomMateo2014IncreasedOS,
  title={Increased Oxidative Stress and Impaired Antioxidant Response in Lafora Disease},
  author={C. Rom{\'a}-Mateo and C. Aguado and J. Garc{\'i}a-Gim{\'e}nez and J. S. Ib{\'a}{\~n}ez-Cabellos and M. Seco-Cervera and F. Pallard{\'o} and E. Knecht and P. Sanz},
  journal={Molecular Neurobiology},
  year={2014},
  volume={51},
  pages={932-946}
}
Lafora disease (LD, OMIM 254780, ORPHA501) is a fatal neurodegenerative disorder characterized by the presence of glycogen-like intracellular inclusions called Lafora bodies and caused, in the vast majority of cases, by mutations in either EPM2A or EPM2B genes, encoding respectively laforin and malin. In the last years, several reports have revealed molecular details of these two proteins and have identified several processes affected in LD, but the pathophysiology of the disease still remains… Expand
Lafora Disease: A Ubiquitination-Related Pathology
TLDR
The possible cellular functions of la forin and malin are reviewed with a special focus on their role in the ubiquitination of specific substrates, as well as the pathological consequences of defects in laforin or malin functions, aswell as the therapeutic strategies that are being explored for LD. Expand
Degradation of altered mitochondria by autophagy is impaired in Lafora disease
TLDR
The autophagic degradation of altered mitochondria is impaired in LD, which is due to a partial defect in the Autophagic response and not in the canonical mitophagy signalling pathways. Expand
Trehalose Ameliorates Seizure Susceptibility in Lafora Disease Mouse Models by Suppressing Neuroinflammation and Endoplasmic Reticulum Stress.
TLDR
It is demonstrated here that trehalose ameliorates gliosis, neuroinflammation, and endoplasmic reticulum stress and reduces susceptibility to induced seizures in LD animals and suggest that autophagy inducers can be considered as potential therapeutic molecules for Lafora disease. Expand
Loss of laforin or malin results in increased Drp1 level and concomitant mitochondrial fragmentation in Lafora disease mouse models
TLDR
The results suggest that laforin and malin are novel regulators of mitochondrial quality control pathway and that the mitochondrial dysfunction resulting from the increased Drp1 levels could underlie neuropathology in LD. Expand
Regulation of the autophagic PI3KC3 complex by laforin/malin E3-ubiquitin ligase, two proteins involved in Lafora disease.
TLDR
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Oxidative Stress, a Crossroad between Rare Diseases and Neurodegeneration
TLDR
The present review aims to expand knowledge in the pathological processes associated with oxidative stress underlying some groups of rare diseases: Friedreich’s ataxia, diseases with neurodegeneration with brain iron accumulation, Charcot-Marie-Tooth as an example of rare neuromuscular disorders, inherited retinal dystrophies, progressive myoclonus epilepsies, and pediatric drug-resistant epilepsy. Expand
A novel EPM2A mutation yields a slow progression form of Lafora disease
TLDR
It is concluded that the slow progression of the disease present in this patient could be either due to the specific biochemical properties of laforin N163D or to the presence of alternative genetic modifying factors separate from pathogenicity. Expand
Biomedical Implications of Autophagy in Macromolecule Storage Disorders
TLDR
The role of autophagy is discussed, which has been shown to improve cell viability and exert beneficial effects in experimental models of various macromolecule storage disorders where the lysosomal functionality is not overtly compromised, and the potential therapeutic benefits of autophile enhancers in these pathological conditions. Expand
Lafora disease: from genotype to phenotype
TLDR
This review attempts to provide a comprehensive coverage on the genetic defects leading to the LD in humans, on the functional properties of the laforin and malin proteins, and on how defects in any one of these two proteins result in a clinically similar phenotype. Expand
Molecular tools for the characterization of seizure susceptibility in genetic rodent models of epilepsy
TLDR
The present review focused on the great diversity of technical approaches available and new research methodology, which are already being used to study molecular alterations underlying epilepsy, and grouped the different techniques according to each step in the flow of information from DNA to RNA to proteins. Expand
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TLDR
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TLDR
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TLDR
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TLDR
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