Home

Person

Hilal Lashuel

This person has left EPFL

About
Privacy
Disclaimer

Graph Chatbot

Related publications (152)

Page 2 of 8

Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synuclein-membrane interactions

Patrick Aebischer, Hilal Lashuel, Bernard Schneider, Marc Moniatte, Diego Chiappe, Adrian Schmid, Abid Oueslati

Increasing evidence suggests that phosphorylation may play an important role in the oligomerization, fibrillogenesis, Lewy body (LB) formation, and neurotoxicity of alpha-synuclein (alpha-syn) in Parkinson disease. Herein we demonstrate that alpha-syn is p ...

2010

The conformational flexibility of the carboxy terminal residues 105-114 is a key modulator of the catalytic activity and stability of macrophage migration inhibitory factor

Ursula Röthlisberger, Hilal Lashuel, Michele Cascella

Macrophage migration inhibitory factor (MIF) is a multifunctional protein and a major mediator of innate immunity. Although X-ray crystallography revealed that MIF exists as a homotrimer, its oligomerization state in vivo and the factors governing its olig ...

American Chemical Society2008

Prominent astrocytic alpha-synuclein pathology with unique post-translational modification signatures unveiled across Lewy body disorders

Hilal Lashuel, Melek Firat Altay

Alpha-synuclein (aSyn) is a pre-synaptic monomeric protein that can form aggregates in neurons in Parkinson's disease (PD), Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB), and in oligodendrocytes in multiple system atrophy (MSA ...

BMC2022

Role of post-translational modifications in modulating the structure, function and toxicity of alpha-synuclein: implications for Parkinson's disease pathogenesis and therapies

Hilal Lashuel, Abid Oueslati

A better understanding of the molecular and cellular determinants that influence the pathology of Parkinson's disease (PD) is essential for developing effective diagnostic, preventative and therapeutic strategies to treat this devastating disease. A number ...

Elsevier2010

Do Lewy bodies contain alpha-synuclein fibrils? and Does it matter? A brief history and critical analysis of recent reports

Hilal Lashuel

Several lines of evidence from neuropathological studies, human genetics, in vitro aggregation studies and cellular and animal models support the hypothesis that aSyn plays a central role in the formation of Lewy pathologies. These are cytoplasmic proteina ...

2020

Huntingtin inclusion bodies have distinct immunophenotypes and ubiquitination profiles in the Huntington’s disease human cerebral cortex

Hilal Lashuel

Huntington's disease (HD) is a hereditary neurodegenerative condition caused by a CAG repeat expansion mutation in the gene encoding the huntingtin (HTT) protein. The accumulation of HTT inclusion bodies is a pathological hallmark of HD and a common target ...

Nature Research2025

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

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

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

Phosphorylation of alpha-Synuclein at Y125 and S129 Alters Its Metal Binding Properties: Implications for Understanding the Role of alpha-Synuclein in the Pathogenesis of Parkinson's Disease and Related Disorders

Hubert Girault, Hilal Lashuel, Michel Prudent, Bruno Claude Daniel Fauvet, Yu Lu

alpha-Synuclein (alpha-syn) is a 140-amino acid protein that plays a central role in the pathogenesis of Parkinson's disease (PD) and other synucleinopathies. However, the molecular determinants that are responsible for triggering and/or propagating alpha- ...

American Chemical Society2011

Glycation potentiates α-synuclein-associated neurodegeneration in synucleinopathies

Hilal Lashuel

α-Synuclein misfolding and aggregation is a hallmark in Parkinson's disease and in several other neurodegenerative diseases known as synucleinopathies. The toxic properties of α-synuclein are conserved from yeast to man, but the precise underpinnings of th ...

Oxford University Press2017

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, Francesco Simone Ruggeri, Anass Chiki, Sean Michael Deguire, Urszula Beata Cendrowska, Ritwik Burai, Annalisa Ansaloni, 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

Chronic corticosterone aggravates behavioral and neuronal symptomatology in a mouse model of alpha-synuclein pathology

Hilal Lashuel, Maria del Carmen Sandi Perez, Johannes Burtscher, Anass Chiki, João Pedro de Matos Rodrigues, Jean-Christophe Copin

Debilitating, yet underinvestigated nonmotor symptoms related to mood/emotion, such as depression, are common in Parkinson's disease. Here, we explore the role of depression and of the amygdala, a brain region robustly linked to mood/emotion, in synucleino ...

2019

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

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

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

Macrophage migration inhibitory factor is critically involved in basal and fluoxetine-stimulated adult hippocampal cell proliferation and in anxiety, depression, and memory-related behaviors

Hilal Lashuel, Maria del Carmen Sandi Perez, Jorge Eduardo Castro Cifuentes

Intensive research is devoted to unravel the neurobiological mechanisms mediating adult hippocampal neurogenesis, its regulation by antidepressants, and its behavioral consequences. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokin ...

Nature Publishing Group2011

Switch-peptides as folding precursors in self-assembling peptides and amyloid fibrillogenesis

Hilal Lashuel, Richard Alan Mimna, Karine Murat, Adrian Schmid, Marie-Stéphanie Camus, Jérémy Bérard

The study of conformational transitions of peptides has obtained considerable attention recently because of their importance as a mol. key event in a variety of degenerative diseases. However, the study of peptide self-assembly into beta-sheets and amyloid ...

2007

Differential Effects of Post-translational Modifications on the Membrane Interaction of Huntingtin Protein

Hilal Lashuel, Matteo Dal Peraro, Luciano Andres Abriata, Charlotte Julie Caroline Gehin, Zhidian Zhang

Huntington's disease is a neurodegenerative disorder caused by an expanded polyglutamine stretch near the N-terminus of the huntingtin (HTT) protein, rendering the protein more prone to aggregate. The first 17 residues in HTT (Nt17) interact with lipid mem ...

Amer Chemical Soc2024

Artificial intelligence-coupled plasmonic infrared sensor for detection of structural protein biomarkers in neurodegenerative diseases

Hilal Lashuel, Hatice Altug, Rajasekhar Kolla, Deepthy Kavungal, Pedro José Santana Ribeiro Magalhães, Senthil Kumar Thangaraj

Diagnosis of neurodegenerative disorders (NDDs) including Parkinson's disease and Alzheimer's disease is challenging owing to the lack of tools to detect preclinical biomarkers. The misfolding of proteins into oligomeric and fibrillar aggregates plays an i ...

AMER ASSOC ADVANCEMENT SCIENCE2023

Protein Semisynthesis Provides Access to Tau Disease-Associated Post-translational Modifications (PTMs) and Paves the Way to Deciphering the Tau PTM Code in Health and Diseased States

Hilal Lashuel, Mahmood Haj Yahya

The microtubule-associated protein Tau plays a central role in neurodegeneration and is a leading therapeutic target for the treatment of Alzheimer’s disease (AD). Several lines of evidence suggest that post-translational modifications (PTMs) regulate the ...

2018

Characterization of semisynthetic and naturally Nα-acetylated α-synuclein in vitro and in intact cells: implications for aggregation and cellular properties of α-synuclein

Hilal Lashuel, Bruno Claude Daniel Fauvet, Mohamed Bilal Fares

N-terminal acetylation is a very common post-translational modification, although its role in regulating protein physical properties and function remains poorly understood. α-Synuclein (α-syn), a protein that has been linked to the pathogenesis of Parkinso ...

Amer Soc Biochemistry Molecular Biology Inc2012

Ultrasensitive quantitative measurement of huntingtin phosphorylation at residue S13

Hilal Lashuel, 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

Alpha-synuclein research: defining strategic moves in the battle against Parkinson's disease

Hilal Lashuel

With the advent of the genetic era in Parkinson's disease (PD) research in 1997, alpha-synuclein was identified as an important player in a complex neurodegenerative disease that affects >10 million people worldwide. PD has been estimated to have an econom ...

NATURE RESEARCH2021