5 documents found, page 1 of 1
RNA Interference Mitigates Motor and Neuropathological Deficits in a Cerebellar...
Nóbrega, Clévio; Nascimento-Ferreira, Isabel; Onofre, Isabel; Albuquerque, David; Déglon, Nicole; Almeida, Luís Pereira deMachado-Joseph disease or Spinocerebellar ataxia type 3 is a progressive fatal neurodegenerative disorder caused by the polyglutamine-expanded protein ataxin-3. Recent studies demonstrate that RNA interference is a promising approach for the treatment of Machado-Joseph disease. However, whether gene silencing at an early time-point is able to prevent the appearance of motor behavior deficits typical of the dise...
Silencing mutant ataxin-3 rescues motor deficits and neuropathology in Machado-...
Nóbrega, Clévio; Nascimento-Ferreira, Isabel; Onofre, Isabel; Albuquerque, David; Hirai, Hirokazu; Déglon, Nicole; Almeida, Luís Pereira deMachado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is an autosomal dominantly-inherited neurodegenerative disorder caused by the over-repetition of a CAG codon in the MJD1 gene. This expansion translates into a polyglutamine tract that confers a toxic gain-of-function to the mutant protein--ataxin-3, leading to neurodegeneration in specific brain regions, with particular severity in the cerebe...
Moderate long-term modulation of neuropeptide Y in hypothalamic arcuate nucleus...
Sousa-Ferreira, Lígia; Garrido, Manuel Joaquim Marques; Nascimento-Ferreira, Isabel; Nóbrega, Clévio; Carvalho, Ana dos SantosNeuropeptide Y (NPY) produced by arcuate nucleus (ARC) neurons has a strong orexigenic effect on target neurons. Hypothalamic NPY levels undergo wide-ranging oscillations during the circadian cycle and in response to fasting and peripheral hormones (from 0.25 to 10-fold change). The aim of the present study was to evaluate the impact of a moderate long-term modulation of NPY within the ARC neurons on food consu...
Allele-specific RNA silencing of mutant ataxin-3 mediates neuroprotection in a ...
Alves, Sandro; Nascimento-Ferreira, Isabel; Auregan, Gwennaëlle; Hassig, Raymonde; Dufour, Noëlle; Brouillet, Emmanuel; Lima, Maria C. Pedroso deRecent studies have demonstrated that RNAi is a promising approach for treating autosomal dominant disorders. However, discrimination between wild-type and mutant transcripts is essential, to preserve wild-type expression and function. A single nucleotide polymorphism (SNP) is present in more than 70% of patients with Machado-Joseph disease (MJD). We investigated whether this SNP could be used to inactivate mut...
Striatal and nigral pathology in a lentiviral rat model of Machado-Joseph disease
Alves, Sandro; Régulier, Etienne; Nascimento-Ferreira, Isabel; Hassig, Raymonde; Dufour, Noelle; Koeppen, Arnulf; Carvalho, Ana Luísa; Simões, SérgioMachado-Joseph disease (MJD) is a fatal, dominant neurodegenerative disorder. MJD results from polyglutamine repeat expansion in the MJD-1 gene, conferring a toxic gain of function to the ataxin-3 protein. In this study, we aimed at overexpressing ataxin-3 in the rat brain using lentiviral vectors (LV), to generate an in vivo MJD genetic model and, to study the disorder in defined brain regions: substantia nigr...