Publications de Anne-Laure Mahul Mellier

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

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

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, Anne-Laure Mahul Mellier, Sonia Donzelli, Ramanath Narayana Hegde, 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

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

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

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

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, 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

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

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

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

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

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