Publications de Sean Michael Deguire

Revisiting the specificity and ability of phospho-S129 antibodies to capture alpha-synuclein biochemical and pathological diversity

Hilal Lashuel, Nicolas Jean Philippe Guex, Christian Iseli, Anne-Laure Mahul Mellier, Jonathan Jean-Pierre Ricci, Yllza Jasiqi, Anass Chiki, Sean Michael Deguire, Ritwik Burai, Melek Firat Altay

Antibodies against phosphorylated alpha-synuclein (aSyn) at 5129 have emerged as the primary tools to investigate, monitor, and quantify aSyn pathology in the brain and peripheral tissues of patients with Parkinson's disease and other neurodegenerative dis ...

NATURE PORTFOLIO2022

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 ...

Elsevier2021

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

Phospho-S129 Alpha-Synuclein Is Present in Human Plasma but Not in Cerebrospinal Fluid as Determined by an Ultrasensitive Immunoassay

Hilal Lashuel, Sean Michael Deguire, Lara Petricca

Accumulation and aggregation of misfolded alpha-synuclein is believed to be a cause of Parkinson's disease (PD). Phosphorylation of alpha-synuclein at S129 is known to be associated with the pathological misfolding process, but efforts to investigate the r ...

2019

N-terminal Huntingtin (Htt) phosphorylation is a molecular switch regulating Htt aggregation, helical conformation, internalization, and nuclear targeting

Giovanni Dietler, Hilal Lashuel, Francesco Simone Ruggeri, Anass Chiki, Mohamed Bilal Fares, Sean Michael Deguire, Urszula Beata Cendrowska

American Society for Biochemistry and Molecular Biology Inc.2018

Polyglutamine 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 Nature2017

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

Hilal Lashuel, Anass Chiki, Lara Petricca, 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

Mutant Exon1 Huntingtin Aggregation is Regulated by T3 Phosphorylation-Induced Structural Changes and Crosstalk between T3 Phosphorylation and Acetylation at K6

Giovanni Dietler, Hilal Lashuel, Anass Chiki, Francesco Simone Ruggeri, Urszula Beata Cendrowska, Annalisa Ansaloni, Ritwik Burai, Sean Michael Deguire, Sophie Vieweg

Herein, we used protein semisynthesis to investigate, for the first time, the effect of lysine acetylation and phosphorylation, as well as the crosstalk between these modifications on the structure and aggregation of mutant huntingtin exon1 (Httex1). Our r ...

Wiley-Blackwell2017