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

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

TBK1 phosphorylates mutant Huntingtin and suppresses its aggregation and toxicity in Huntington's disease models

Johan Auwerx, Hilal Lashuel, Laurent Mouchiroud, Lara Petricca, Anass Chiki, Ramanath Narayana Hegde

Phosphorylation of the N‐terminal domain of the huntingtin (HTT ) protein has emerged as an important regulator of its localization, structure, aggregation, clearance and toxicity. However, validation of the effect of bona fide phosphorylation in vivo and ...

2020

The 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 PRESS2020

Site-Specific Phosphorylation of Huntingtin Exon 1 Recombinant Proteins Enabled by the Discovery of Novel Kinases

Hilal Lashuel, Luciano Andres Abriata, Jonathan Jean-Pierre Ricci, Anass Chiki, Andreas Reif, Driss Boudeffa

Post-translational modifications (PTMs) within the first 17 amino acids (Nt17) of exon 1 of the Huntingtin protein (Httex1) play important roles in modulating its cellular properties and functions in health and disease. In particular, phosphorylation of th ...

2020

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

Medium chain triglyceride diet reduces anxiety-like behaviors and enhances social competitiveness in rats

Maria del Carmen Sandi Perez, Carlos Canto Alvarez, Fiona Hollis

Medium-chain triglycerides (MCT) are emerging as unique dietary supplements that are potentially relevant for the amelioration of brain dysfunctions. MCT are converted into ketones and free medium chain fatty acids that, in the brain, are highly effective ...

2018

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

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

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

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

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

TBK1 phosphorylates mutant Huntingtin and suppresses its aggregation and toxicity in Huntington's disease models

The Polyglutamine Expansion at the N-Terminal of Huntingtin Protein Modulates the Dynamic Configuration and Phosphorylation of the C-Terminal HEAT Domain

Site-Specific Phosphorylation of Huntingtin Exon 1 Recombinant Proteins Enabled by the Discovery of Novel Kinases

Ultrasensitive quantitative measurement of huntingtin phosphorylation at residue S13

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

Medium chain triglyceride diet reduces anxiety-like behaviors and enhances social competitiveness in rats

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

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

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

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Site-Specific Phosphorylation of Huntingtin Exon 1 Recombinant Proteins Enabled by the Discovery of Novel Kinases

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

TBK1 phosphorylates mutant Huntingtin and suppresses its aggregation and toxicity in Huntington's disease models

The Polyglutamine Expansion at the N-Terminal of Huntingtin Protein Modulates the Dynamic Configuration and Phosphorylation of the C-Terminal HEAT Domain

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

Ultrasensitive quantitative measurement of huntingtin phosphorylation at residue S13

Medium chain triglyceride diet reduces anxiety-like behaviors and enhances social competitiveness in rats

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

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

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