Publications de Anne-Laure Mahul Mellier

Differential role of C-terminal truncations on alpha-synuclein pathology and Lewy body formation

Graham Knott, Mary-Claude Croisier-Coeytaux, Anass Chiki, Nadine Aït Bouziad, Romain Hamelin, Anne-Laure Mahul Mellier, Niran Maharjan, Melek Firat Altay, Jonathan Jean-Pierre Ricci, Somanath Jagannath, Galina Limorenko, Salvatore Novello, Yllza Jasiqi

Alpha-synuclein (aSyn) post-translational modifications (PTM), especially phosphorylation at serine 129 and C-terminal truncations, are highly enriched in Lewy bodies (LB), Lewy neurites, and other pathological aggregates in Parkinson's disease and synucle ...

Springer Science and Business Media LLC2025

Emerging disease-modifying therapies for Parkinson’s disease Nouvelles stratégies thérapeutiques dans la maladie de Parkinson

Anne-Laure Mahul Mellier

Despite extensive clinical research, no disease-modifying treatment has been proven to alter the progression of Parkinson’s disease (PD). However, recent decades have seen significant advances in understanding its underlying neurodegenerative mechanisms, r ...

2025

A NAC domain mutation (E83Q) unlocks the pathogenicity of human alpha-synuclein and recapitulates its pathological diversity

Hilal Lashuel, Ramanath Narayana Hegde, Anne-Laure Mahul Mellier, Sonia Donzelli, Pedro José Santana Ribeiro Magalhães

The alpha-synuclein mutation E83Q, the first in the NAC domain of the protein, was recently identified in a patient with dementia with Lewy bodies. We investigated the effects of this mutation on the aggregation of aSyn monomers and the structure, morpholo ...

AMER ASSOC ADVANCEMENT SCIENCE2022

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

Christian Iseli, Nicolas Jean Philippe Guex, Hilal Lashuel, Anass Chiki, Ramanath Narayana Hegde, Anne-Laure Mahul Mellier, Ritwik Burai, Sean Michael Deguire, Melek Firat Altay, Sonia Donzelli, Jonathan Jean-Pierre Ricci, Salvatore Novello, Pedro José Santana Ribeiro Magalhães, Yllza Jasiqi

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

Nuclear and cytoplasmic huntingtin inclusions exhibit distinct biochemical composition, interactome and ultrastructural properties

Graham Knott, Hilal Lashuel, Mary-Claude Croisier-Coeytaux, Anne-Laure Mahul Mellier, Niran Maharjan, Johannes Burtscher, Nathan Alain Denis Riguet

Despite the strong evidence linking the aggregation of the Huntingtin protein (Htt) to the pathogenesis of Huntington’s disease (HD), the mechanisms underlying Htt aggregation and neurodegeneration remain poorly understood. Herein, we investigated the ultr ...

Springer Nature2021

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, Sophie Vieweg, Sean Michael Deguire, Urszula Beata Cendrowska, 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

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

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

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

alpha-Synuclein O-GlcNAcylation alters aggregation and toxicity, revealing certain residues as potential inhibitors of Parkinson's disease

Hilal Lashuel, Anne-Laure Mahul Mellier

A compelling link is emerging between the posttranslational modification O-GlcNAc and protein aggregation. A prime example is alpha-synuclein, which forms toxic aggregates that are associated with neurodegeneration in Parkinson's and related diseases. alph ...

National Academy of Sciences2019

Combined Multi-Plane Tomographic Phase Retrieval and Stochastic Optical Fluctuation Imaging for 4D Cell Microscopy

Marcel Leutenegger, Theo Lasser, Hilal Lashuel, Adrien Charles-François Raymond Descloux, Emrah Bostan, Arno Pino Bouwens, Anne-Laure Mahul Mellier, Tomas Lukes

Super-resolution fluorescence microscopy provides unprecedented insight into cellular and subcellular structures. However, going beyond the diffraction barrier comes at a price since most far-field super-resolution imaging techniques trade temporal for spa ...

Nature Publishing Group2018

Discovery and characterization of novel stable tau oligomeric complexes: Implications for the role of Tau/phospholipid interactions in regulating its functions in health and disease

Hilal Lashuel, Nadine Aït Bouziad, Gizem Zorludemir, Anne-Laure Mahul Mellier

The microtubule-associated protein Tau plays a central role in the pathogenesis of Alzheimer's disease. Although Tau interaction with membranes is thought to affect some of its physiological functions and its aggregation properties, the sequence determinan ...

Nature Publishing Group2017

Amyloid Single Cell Cytotoxicity Assays by Nanomotion Detection

Giovanni Dietler, Sandor Kasas, Hilal Lashuel, Giovanni Longo, Francesco Simone Ruggeri, Anne-Laure Mahul Mellier

Cells are extremely complex systems able to modify actively their metabolism and behaviour in response to environmental conditions and stimuli, such as pathogenic agents or drugs. The comprehension of these responses is central to understand the molecular ...

Springer Nature2017

Semisynthetic and in Vitro Phosphorylation of Alpha-Synuclein at Y39 Promotes Functional Partly Helical Membrane-Bound States Resembling Those Induced by PD Mutations

Bruno Claude Daniel Fauvet, Hilal Lashuel, Farah El Turk, Ana Jovicic, Carole Desobry, Anne-Laure Mahul Mellier

Alpha-synuclein is a presynaptic protein of poorly understood function that is linked to both genetic and sporadic forms of Parkinson's disease. We have proposed that alpha-synuclein may function specifically at synaptic vesicles docked at the plasma membr ...

Amer Chemical Soc2016

Stefan Grimm, 1963-2014, a tragic loss for the scientific community Obituary

Anne-Laure Mahul Mellier

Nature Publishing Group2015

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

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

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