Publication

Sustained Effects of Nonallele-Specific Huntingtin Silencing

Publications associées (30)

Transcriptional dysregulation in Huntington's disease

Huntington's disease (HD) is a progressive neurodegenerative disorder with autosomal dominant inheritance. It is caused by a singular mutation in exon 1 of the HD gene encoding an abnormal polyglutamine (polyQ) expansion in the N-terminal region of the hun ...

EPFL2008

Dysregulation of gene expression in primary neuron models of Huntington's disease shows that polyglutamine-related effects on the striatal transcriptome may not be dependent on brain circuitry

Diana Zala, Patrick Aebischer, Valérie Gafner, Nicole Déglon, Heike Runne, Ozgün Gökce

Gene expression changes are a hallmark of the neuropathology of Huntington's disease (HD), but the exact molecular mechanisms of this effect remain uncertain. Here, we report that in vitro models of disease comprised of primary striatal neurons expressing ...

2008

Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage

Thierry Sengstag, Darlene Goldstein, Mauro Delorenzi

To test the hypotheses that mutant huntingtin protein length and wild-type huntingtin dosage have important effects on disease-related transcriptional dysfunction, we compared the changes in mRNA in seven genetic mouse models of Huntington's disease (HD) a ...

Oxford University Press2007

Altering protein folding, intracellular signaling, or the post-transcriptional program as potential therapeutic strategies to counteract Huntington's disease

Valérie Gafner

Huntington's disease (HD) is an autosomal, dominantly inherited neurodegenerative disorder caused by expansion of a glutamine (polyQ) repeat in the huntingtin (htt) protein. The selective striatal neurodegeneration induced by this disease causes choreic in ...

EPFL2006

Inhibition of calcineurin by FK506 protects against polyglutamine-huntingtin toxicity through an increase of huntingtin phosphorylation at S421

Patrick Aebischer, Nicole Déglon

Huntington's disease (HD) is caused by an abnormal expanded polyglutamine (polyQ) repeat in the huntingtin protein. Insulin-like growth factor-1 acting through the prosurvival kinase Akt mediates the phosphorylation of huntingtin at S421 and inhibits the t ...

2006

Huntington's disease modeling and treatment : from primary neuronal cultures to rodents

Diana Zala

Huntington's disease (HD) is a mid-life-onset neurodegenerative disorder characterized by involuntary movements, personality changes and dementia. It progresses to death within 10-20 years after onset. There is currently no cure to treat this fatal disease ...

EPFL2005

Progressive and selective striatal degeneration in primary neuronal cultures using lentiviral vector coding for a mutant huntingtin fragment

Diana Zala, Patrick Aebischer, Valérie Gafner, Nicole Déglon

A lentiviral vector expressing a mutant huntingtin protein (htt171-82Q) was used to generate a chronic model of Huntington's disease (HD) in rat primary striatal cultures. In this model, the majority of neurons expressed the transgene so that Western blot ...

2005

Early and reversible neuropathology induced by tetracycline-regulated lentiviral overexpression of mutant huntingtin in rat striatum

Patrick Aebischer, Valérie Gafner, Nicole Déglon

The ability to overexpress full-length huntingtin or large fragments represents an important challenge to mimic Huntington's pathology and reproduce all stages of the disease in a time frame compatible with rodent life span. In the present study, tetracycl ...

Oxford University Press2003

Lentiviral-mediated delivery of mutant huntingtin in the striatum of rats induces a selective neuropathology modulated by polyglutamine repeat size, huntingtin expression levels, and protein length

Diana Zala, Patrick Aebischer, Nicole Déglon

A new strategy based on lentiviral-mediated delivery of mutant huntingtin (htt) was used to create a genetic model of Huntington's disease (HD) in rats and to assess the relative contribution of polyglutamine (CAG) repeat size, htt expression levels, and p ...

2002

Lentiviral-mediated RNA interference

Patrick Aebischer, Nicole Déglon

RNA interference (RNAi) is a form of posttranscriptional gene silencing mediated by short double-stranded RNA, known as small interfering RNA (siRNA). These siRNAs are capable of binding to a specific mRNA sequence and causing its degradation. The recent d ...

2002