Concept

Huntingtin

Related publications (53)

Reanalysis of mtDNA mutations of human primordial germ cells (PGCs) reveals NUMT contamination and suggests that selection in PGCs may be positive

The resilience of the mitochondrial genome (mtDNA) to a high mutational pressure depends, in part, on negative purifying selection in the germline. A paradigm in the field has been that such selection, at least in part, takes place in primordial germ cells ...

London2023

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 SCIENCE2022

An integrative approach to elucidate the mechanisms and dynamics of Huntingtin aggregation and inclusion formation in neuronal models of Huntington's Disease

Nathan Alain Denis Riguet

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 ...

EPFL2022

A 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 ...

2021

Pharmacological characterization of mutant huntingtin aggregate-directed PET imaging tracer candidates

Hilal Lashuel, Anass Chiki

Huntington's disease (HD) is caused by a CAG trinucleotide repeat expansion in the first exon of the huntingtin (HTT) gene coding for the huntingtin (HTT) protein. The misfolding and consequential aggregation of CAG-expanded mutant HTT (mHTT) underpin HD p ...

NATURE PORTFOLIO2021

Enforced dimerization between XBP1s and ATF6f enhances the protective effects of the UPR in models of neurodegeneration

Hilal Lashuel

Alteration to endoplasmic reticulum (ER) proteostasis is observed in a variety of neurodegenerative diseases associated with abnormal protein aggregation. Activation of the unfolded protein response (UPR) enables an adaptive reaction to recover ER proteost ...

2021

Investigating Crosstalk Among PTMs Provides Novel Insight Into the Structural Basis Underlying the Differential Effects of Nt17 PTMs on Mutant Httex1 Aggregation

Hilal Lashuel, Matteo Dal Peraro, Luciano Andres Abriata, Lucien Fabrice Krapp, Anass Chiki, Iman Rostami, Driss Boudeffa, Zhidian Zhang

Post-translational modifications (PTMs) within the first 17 amino acids (Nt17) of the Huntingtin protein (Htt) have been shown to inhibit the aggregation and attenuate the toxicity of mutant Htt proteins in vitro and in various models of Huntington’s disea ...

2021

The Nt17 Domain and its Helical Conformation Regulate the Aggregation, Cellular Properties and Neurotoxicity of Mutant Huntingtin Exon 1

Giovanni Dietler, Hilal Lashuel, Anne-Laure Mahul Mellier, Francesco Simone Ruggeri, Anass Chiki, Sean Michael Deguire, Urszula Beata Cendrowska, Sophie Vieweg, Nathan Alain Denis Riguet

Converging evidence points to the N-terminal domain comprising the first 17 amino acids of the Huntingtin protein (Nt17) as a key regulator of its aggregation, cellular properties and toxicity. In this study, we further investigated the interplay between N ...

2021

Development of novel methods and tools to decipher the huntingtin post-translation modifications code

Anass Chiki

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 ...

EPFL2020

Ultrasensitive 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 SCIENCE2020

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