Publication
Generation of Native, Untagged Huntingtin Exon1 Monomer and Fibrils Using a SUMO Fusion Strategy
Related publications (34)
N-terminal mutant huntingtin deposition correlates with CAG repeat length and symptom onset, but not neuronal loss in Huntington's disease
Hilal Lashuel, Lorène Aeschbach, Nathan Alain Denis Riguet
Huntington's disease (HD) is caused by a CAG repeat expansion mutation in the gene encoding the huntingtin (Htt) protein, with mutant Htt protein subsequently forming aggregates within the brain. Mutant Htt is a current target for novel therapeutic strateg ...
ACADEMIC PRESS INC ELSEVIER SCIENCE2022An integrative approach to elucidate the mechanisms and dynamics of Huntingtin aggregation and inclusion formation in neuronal models of Huntington's Disease
Despite the fact that the gene responsible for Huntington's disease (HD) is known, we still do not understand the underlying mechanisms leading to neurodegeneration and death. Identifying and understanding the mechanisms controlling mutant huntingtin (mHtt ...
EPFL2022A New Chemoenzymatic Semisynthetic Approach Provides Insight into the Role of Phosphorylation beyond Exon1 of Huntingtin and Reveals N-Terminal Fragment Length-Dependent Distinct Mechanisms of Aggregation
Hilal Lashuel, Jonathan Jean-Pierre Ricci, Andreas Reif, Iman Rostami, Rajasekhar Kolla, Gopinath Pushparathinam
Huntington’s disease is a neurodegenerative dis- order caused by the expansion of a polyglutamine repeat (>36Q) in the N-terminal domain of the huntingtin protein (Htt), which renders the protein or fragments thereof more prone to aggregate and form inclus ...
2021Development of novel methods and tools to decipher the huntingtin post-translation modifications code
Huntington's disease (HD) is a fatal genetic neurodegenerative disorder caused by a CAG repeat expansion in the Huntingtin gene of more than 36 repeats. This repeat is translated into a polyglutamine (polyQ) stretch within the first exon-encoded region of ...
EPFL2020Ultrasensitive quantitative measurement of huntingtin phosphorylation at residue S13
Hilal Lashuel, Lara Petricca, Sean Michael Deguire
Huntington's disease (HD) is a progressive neurodegenerative disorder caused by an expansion of a CAG triplet repeat (encoding for a polyglutamine tract) within the first exon of the huntingtin gene. Expression of the mutant huntingtin (mHTT) protein can r ...
ACADEMIC PRESS INC ELSEVIER SCIENCE2020The Polyglutamine Expansion at the N-Terminal of Huntingtin Protein Modulates the Dynamic Configuration and Phosphorylation of the C-Terminal HEAT Domain
Matteo Dal Peraro, Maria Josefina Marcaida Lopez, Giorgio Elikem Tamo, Ruedi Aebersold
The polyQ expansion in huntingtin protein (HTT) is the prime cause of Huntington's disease (HD). The recent cryoelectron microscopy (cryo-EM) structure of HTT-HAP40 complex provided the structural information on its HEAT-repeat domains. Here, we present an ...
CELL PRESS2020Properties of LINE-1 proteins and repeat element expression in the context of amyotrophic lateral sclerosis
Didier Trono, Priscilla Turelli, Evaristo Jose Planet Letschert
BackgroundAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving loss of motor neurons and having no known cure and uncertain etiology. Several studies have drawn connections between altered retrotransposon expression and ALS. C ...
2018Polyglutamine expansion affects huntingtin conformation in multiple Huntington’s disease models
Hilal Lashuel, Lara Petricca, 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 Nature2017The role of the polyglutamine and N-terminal domains in regulating the aggregation and structural properties of Huntingtin Exon 1
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 ...
EPFL2017Monomeric 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