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Concept

Maladie de Huntington

Publications associées (31)

Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy

Hilal Lashuel, Anass Chiki, Jonathan Jean-Pierre Ricci, Andreas Reif

Huntington’s Disease (HD) is an inherited fatal neurodegenerative disease caused by a CAG expansion (36) in the first exon of the HD gene, resulting in the expression of the Huntingtin protein (Htt) or N-terminal fragments thereof with an expanded polygl ...

2018

Polyglutamine expansion affects huntingtin conformation in multiple Huntington’s disease models

Hilal Lashuel, Sean Michael Deguire

Conformational changes in disease-associated or mutant proteins represent a key pathological aspect of Huntington's disease (HD) and other protein misfolding diseases. Using immunoassays and biophysical approaches, we and others have recently reported that ...

Springer Nature2017

Monomeric Huntingtin Exon 1 Has Similar Overall Structural Features for Wild-Type and Pathological Polyglutamine Lengths

Hilal Lashuel, John Blaine Warner IV

Huntington’s disease is caused by expansion of a polyglutamine (polyQ) domain within exon 1 of the huntingtin gene (Httex1). A popular hypothesis is that the Httex1 protein undergoes sharp conformational changes as the polyQ length exceeds a threshold of 3 ...

2017

The role of the polyglutamine and N-terminal domains in regulating the aggregation and structural properties of Huntingtin Exon 1

Sophie Vieweg

Huntington Disease (HD) is caused by a CAG repeat expansion in the huntingtin gene leading to the formation of mutant Huntingtin protein (Htt) with an expanded polyglutamine (polyQ) domain (>36Q). Generation of short N-terminal Htt fragments by proteolysis ...

EPFL2017

Phosphorylation of huntingtin at residue T3 is decreased in Huntington’s disease and modulates mutant huntingtin protein conformation

Hilal Lashuel, Anass Chiki, Sean Michael Deguire

Posttranslational modifications can have profound effects on the biological and biophysical properties of proteins associated with misfolding and aggregation. However, their detection and quantification in clinical samples and an understanding of the mecha ...

2017

Cytoplasmic Ubiquitin-Specific Protease 19 (USP19) Modulates Aggregation of Polyglutamine-Expanded Ataxin-3 and Huntingtin through the HSP90 Chaperone

Françoise Gisou van der Goot Grunberg

Ubiquitin-specific protease 19 (USP19) is one of the deubiquitinating enzymes (DUBs) involved in regulating the ubiquitination status of substrate proteins. There are two major isoforms of USP19 with distinct C-termini; the USP19_a isoform has a transmembr ...

Public Library of Science2016

Nanoscale studies link amyloid maturity with polyglutamine diseases onset

Hilal Lashuel, Giovanni Dietler, Giovanni Longo, Francesco Simone Ruggeri, Urszula Beata Cendrowska

The presence of expanded poly-glutamine (polyQ) repeats in proteins is directly linked to the pathogenesis of several neurodegenerative diseases, including Huntington's disease. However, the molecular and structural basis underlying the increased toxicity ...

Nature Research2016

An Intein-based Strategy for the Production of Tag-free Huntingtin Exon 1 Proteins Enables New Insights into the Polyglutamine Dependence of Httex1 Aggregation and Fibril Formation

Hilal Lashuel, Annalisa Ansaloni, Sophie Vieweg, John Blaine Warner IV

The first exon of the Huntingtin protein (Httex1) is one of the most actively studied Htt fragments because its overexpression in R6/2 transgenic mice has been shown to recapitulate several key features of Huntington disease. However, the majority of bioph ...

Amer Soc Biochemistry Molecular Biology Inc2016

SIRT2-and NRF2-Targeting Thiazole-Containing Compound with Therapeutic Activity in Huntington's Disease Models

There are currently no disease-modifying therapies for the neurodegenerative disorder Huntington's disease (HD). This study identified novel thiazole-containing inhibitors of the deacetylase sirtuin-2 (SIRT2) with neuroprotective activity in ex vivo brain ...

Cell Press2016

LRH-1-dependent programming of mitochondrial glutamine processing drives liver cancer

Johan Auwerx, Arnaud Comment, Kristina Schoonjans, Dongryeol Ryu, Norman Lionel Moullan, Emine Can, Xu Wang, Maaike Hélène Oosterveer, Pan Xu, Hadrien Charles Edouard Demagny

Various tumors develop addiction to glutamine to support uncontrolled cell proliferation. Here we identify the nuclear receptor liver receptor homolog 1 (LRH-1) as a key regulator in the process of hepatic tumorigenesis through the coordination of a noncan ...

Cold Spring Harbor Laboratory2016

An Extended, Boolean Model of the Septation Initiation Network in S-pombe Provides Insights into Its Regulation

Viesturs Simanis, Andrea Krapp

Cytokinesis in fission yeast is controlled by the Septation Initiation Network (SIN), a protein kinase signaling network using the spindle pole body as scaffold. In order to describe the qualitative behavior of the system and predict unknown mutant behavio ...

Public Library of Science2015