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Hilal Lashuel

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Related publications (152)

Page 4 of 8

A century-old debate on protein aggregation and neurodegeneration enters the clinic

Hilal Lashuel

The correlation between neurodegenerative disease and protein aggregation in the brain has long been recognized, but a causal relationship has not been unequivocally established, in part because a discrete pathogenic aggregate has not been identified. The ...

2006

Single Posttranslational Modifications in the Central Repeat Domains of Tau4 Impact its Aggregation and Tubulin Binding

Hilal Lashuel, Mahmood Haj Yahya

A variety of methods have been employed to study the impact of posttranslational modifications on Tau protein function. Here, a semisynthesis strategy is described that enables selective modification within the central repeat domain of Tau4 (residues 291-3 ...

Wiley-VCH Verlag GmbH2019

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

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

Photobiomodulation Suppresses Alpha-Synuclein-Induced Toxicity in an AAV-Based Rat Genetic Model of Parkinson's Disease

Hubert van den Bergh, Georges Wagnières, Hilal Lashuel, Blaise Lovisa, Abid Oueslati

Converging lines of evidence indicate that near-infrared light treatment, also known as photobiomodulation (PBM), may exert beneficial effects and protect against cellular toxicity and degeneration in several animal models of human pathologies, including n ...

Public Library of Science2015

Alpha-synuclein as a Potential Biomarker for Parkinson’s Disease and Other Synucleinopathies: Gaps, Challenges, and Opportunities

Hilal Lashuel, Pedro José Santana Ribeiro Magalhães

Parkinson's disease (PD), the second most common progressive neurodegenerative disease, develops and progresses for 10-15 years before the clinical diagnostic symptoms of the disease are manifested. Furthermore, several aspects of PD pathology overlap with ...

2022

A user's guide for α-synuclein biomarker studies in biological fluids: Perianalytical considerations

Hilal Lashuel

Parkinson's disease biomarkers are needed to increase diagnostic accuracy, to objectively monitor disease progression and to assess therapeutic efficacy as well as target engagement when evaluating novel drug and therapeutic strategies. This article summar ...

Wiley-Blackwell2017

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

Hilal Lashuel, Sonia Donzelli

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

Fully co-factor-free ClearTau platform produces seeding-competent Tau fibrils for reconstructing pathological Tau aggregates

Hilal Lashuel, Henning Paul-Julius Stahlberg, Galina Limorenko, Rajasekhar Kolla, Meltem Tatli

The authors report a method for producing co-factor-free fibrils from all full-length Tau isoforms. The method paves the way for reconstituting pathology resembling Tau fibrils and enables screening of Tau aggregation-modifying compounds for targeted thera ...

Nature Research2023

O-GlcNAc forces an α-synuclein amyloid strain with notably diminished seeding and pathology

Hilal Lashuel, Yllza Jasiqi

Amyloid-forming proteins such alpha-synuclein and tau, which are implicated in Alzheimer's and Parkinson's disease, can form different fibril structures or strains with distinct toxic properties, seeding activities and pathology. Understanding the determin ...

Nature Portfolio2024

Reactive oxidative species enhance amyloid toxicity in APP/PS1 mouse neurons

Hilal Lashuel

To investigate whether intracellular amyloid beta (iA beta) induces toxicity in wild type (WT) and APP/PS1 mice, a mouse model of Alzheimer's disease. ...

2012

Amyloidogenic protein-membrane interactions: mechanistic insight from model systems

Hilal Lashuel

The toxicity of amyloid-forming proteins is correlated with their interactions with cell membranes. Binding events between amyloidogenic proteins and membranes result in mutually disruptive structural perturbations, which are associated with toxicity. Memb ...

2010

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

Effective Inhibition of TDP-43 Aggregation by Native State Stabilization

Hilal Lashuel, Yllza Jasiqi, Lixin Yang

Preventing the misfolding or aggregation of transactive response DNA binding protein with 43 kDa (TDP-43) is the most actively pursued disease-modifying strategy to treat amyotrophic lateral sclerosis and other neurodegenerative diseases. In this work, we ...

Wiley-VCH Verlag GmbH2024

Lewy body-associated proteins: Victims, instigators, or innocent bystanders? The case of AIMP2 and alpha-synuclein

Hilal Lashuel, Salvatore Novello

Lewy bodies (LBs), one of the neuropathological defining hallmarks of Parkinson's disease (PD), are composed of a complex mixture of alpha-synuclein (aSyn) filaments and hundreds of proteins, lipids, and membranous organelles. However, these proteins' role ...

2021

Self-driving microscopy detects the onset of protein aggregation and enables intelligent Brillouin imaging

Camille Valentine Cathala, Hilal Lashuel, Aleksandra Radenovic, Lely Feletti, Khalid Ashraf Mohie Ibrahim

The process of protein aggregation, central to neurodegenerative diseases like Huntington’s, is challenging to study due to its unpredictable nature and relatively rapid kinetics. Understanding its biomechanics is crucial for unraveling its role in disease ...

Springer Science and Business Media LLC2025

The process of Lewy body formation, rather than simply α-synuclein fibrillization, is one of the major drivers of neurodegeneration

Laura Emmeline H Weerens, Hilal Lashuel, Graham Knott, Johannes Burtscher, Marion Leleu, Fabien Kuttler, Mary-Claude Croisier-Coeytaux, Anne-Laure Mahul Mellier, Niran Maharjan

Parkinson’s disease (PD) is characterized by the accumulation of misfolded and aggregated α-synuclein (α-syn) into intraneuronal inclusions named Lewy bodies (LBs). Although it is widely believed that α-syn plays a central role in the pathogenesis of PD, t ...

National Academy of Sciences2020

Neuronal growth on high-aspect-ratio diamond nanopillar arrays for biosensing applications

Hilal Lashuel, Niels Quack, Christophe Marcel Georges Galland, Somanath Jagannath, Maurizio Ferdinando Pezzoli, Elena Losero, Hossein Babashah, Valentin Luc Adrien Goblot

Monitoring neuronal activity with simultaneously high spatial and temporal resolution in living cell cultures is crucial to advance understanding of the development and functioning of our brain, and to gain further insights in the origin of brain disorders ...

Nature Portfolio2023

A Versatile Method for Site-Specific Chemical Installation of Aromatic Posttranslational Modification Analogs into Proteins

Bouchra Bouri, Hilal Lashuel, Rajasekhar Kolla, Shaswati Mandal

Posttranslational modifications (PTMs) of proteins play central roles in regulating the protein structure, interactome, and functions. A notable modification site is the aromatic side chain of Tyr, which undergoes modifications such as phosphorylation and ...

2024

The H50Q Mutation Enhances alpha-Synuclein Aggregation, Secretion, and Toxicity

Hilal Lashuel, Giovanni Dietler, Bruno Claude Daniel Fauvet, Francesco Simone Ruggeri, Anne-Laure Mahul Mellier, Abid Oueslati, Martial Mbefo Kamdem, Ossama Mohamed Salah El-Dien El-Sayed Ibrahim Khalaf, Filip Vercruysse

Over the last two decades, the identification of missense mutations in the alpha-synuclein (alpha-Syn) gene SNCA in families with inherited Parkinson disease (PD) has reinforced the central role of alpha-Syn in PD pathogenesis. Recently, a new missense mut ...

American Society for Biochemistry and Molecular Biology2014

Research Priorities on the Role of α-Synuclein in Parkinson's Disease Pathogenesis

Hilal Lashuel

Various forms of Parkinson's disease, including its common sporadic form, are characterized by prominent α-synuclein (αSyn) aggregation in affected brain regions. However, the role of αSyn in the pathogenesis and evolution of the disease remains unclear, d ...

2024