Improvement of BDNF signalling by P42 peptide in Huntington's disease.

Huntington's disease (HD) is caused by a mutation in the Huntingtin (HTT) protein. We previously reported that the 23aa peptide of HTT protein, P42, is preventing HD pathological phenotypes, such as aggregation, reduction of motor performances and neurodegeneration. A systemic treatment with P42 during the pre-symptomatic phase of the disease showed therapeutic potential in R6/2 mice.

Control of nerve cord formation by Engrailed and Gooseberry-Neuro: A multi-step, coordinated process.

One way to better understand the molecular mechanisms involved in the construction of a nervous system is to identify the downstream effectors of major regulatory proteins. We previously showed that Engrailed (EN) and Gooseberry-Neuro (GsbN) transcription factors act in partnership to drive the formation of posterior commissures in the central nervous system of Drosophila. In this report, we identified genes regulated by both EN and GsbN through chromatin immunoprecipitation ("ChIP on chip") and transcriptome experiments, combined to a genetic screen relied to the gene dose titration method.

Systemic delivery of P42 peptide: a new weapon to fight Huntington's disease.

Background: In Huntington's disease (HD), the ratio between normal and mutant Huntingtin (polyQ-hHtt) is crucial in the onset and progression of the disease. As a result, addition of normal Htt was shown to improve polyQ-hHtt-induced defects. Therefore, we recently identified, within human Htt, a 23aa peptide (P42) that prevents aggregation and polyQ-hHtt-induced phenotypes in HD Drosophila model.

A huntingtin peptide inhibits polyQ-huntingtin associated defects.

Background: Huntington's disease (HD) is caused by the abnormal expansion of the polyglutamine tract in the human Huntingtin protein (polyQ-hHtt). Although this mutation behaves dominantly, huntingtin loss of function also contributes to HD pathogenesis. Indeed, wild-type Huntingtin plays a protective role with respect to polyQ-hHtt induced defects.

Induction of ASAP (MAP9) contributes to p53 stabilization in response to DNA damage.

p53 is a key tumor suppressor that controls DNA damage response and genomic integrity. In response to genotoxic stress, p53 is stabilized and activated, resulting in controlled activation of genes involved in cell cycle arrest, DNA repair and/or apoptosis. ASAP is a centrosome- and spindle-associated protein, the deregulation of which induces severe mitotic defects.