Publications by Anass Chiki | EPFL Graph Search

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

Deep Learning-Assisted Single-Molecule Detection of Protein Post-translational Modifications with a Biological Nanopore

Hilal Lashuel, Anass Chiki, Juan Francisco Bada Juarez, Matteo Dal Peraro, Lucien Fabrice Krapp, Chan Cao, Simon Finn Mayer, Pedro José Santana Ribeiro Magalhães

Protein post-translational modifications (PTMs) play a crucial role in countless biological processes, profoundly modulating protein properties on both spatial and temporal scales. Protein PTMs have also emerged as reliable biomarkers for several diseases. ...

Amer Chemical Soc2023

The role of PTM crosstalks in Httex1 structure, aggregation and membrane interaction

Hilal Lashuel, Anass Chiki, Matteo Dal Peraro, Luciano Andres Abriata, Lucien Fabrice Krapp, Driss Boudeffa, Rajasekhar Kolla, Charlotte Julie Caroline Gehin, Zhidian Zhang

CELL PRESS2022

Structural Basis of Huntingtin Fibril Polymorphism Revealed by Cryogenic Electron Microscopy of Exon 1 HTT Fibrils

Hilal Lashuel, Anass Chiki, Sergey Nazarov, Driss Boudeffa

The lack of detailed insight into the structure of aggregates formed by the huntingtin protein (HTT) has hampered the efforts to develop therapeutics and diagnostics targeting pathology formation in the brain of patients with Huntington's disease. To addre ...

2022

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

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

Investigating Crosstalk Among PTMs Provides Novel Insight Into the Structural Basis Underlying the Differential Effects of Nt17 PTMs on Mutant Httex1 Aggregation

Hilal Lashuel, Anass Chiki, Matteo Dal Peraro, Luciano Andres Abriata, Lucien Fabrice Krapp, Driss Boudeffa, Rajasekhar Kolla, Zhidian Zhang, Iman Rostami

Post-translational modifications (PTMs) within the first 17 amino acids (Nt17) of the Huntingtin protein (Htt) have been shown to inhibit the aggregation and attenuate the toxicity of mutant Htt proteins in vitro and in various models of Huntington’s disea ...

2021

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

TBK1 phosphorylates mutant Huntingtin and suppresses its aggregation and toxicity in Huntington's disease models

Hilal Lashuel, Anass Chiki, Johan Auwerx, Ramanath Narayana Hegde, Laurent Mouchiroud, Lara Petricca

Phosphorylation of the N‐terminal domain of the huntingtin (HTT ) protein has emerged as an important regulator of its localization, structure, aggregation, clearance and toxicity. However, validation of the effect of bona fide phosphorylation in vivo and ...

2020

A simple, versatile and robust centrifugation-based filtration protocol for the isolation and quantification of alpha-synuclein monomers, oligomers and fibrils: Towards improving experimental reproducibility in alpha-synuclein research

Hilal Lashuel, Anass Chiki, Sonia Donzelli, Muhammed Muazzam Kamil Syed

Increasing evidence suggests that the process of alpha-synuclein (alpha-syn) aggregation from monomers into amyloid fibrils and Lewy bodies, via oligomeric intermediates plays an essential role in the pathogenesis of different synucleinopathies, including ...

Wiley-Blackwell2020

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

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

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

Unraveling the complexity of amyloid polymorphism using gold nanoparticles and cryo-EM

Hilal Lashuel, Anass Chiki, Nadine Aït Bouziad, Francesco Stellacci, Paulo Henrique Jacob Silva, Marie Mueller, Zekiye Pelin Güven, Sophie Vieweg, Urszula Beata Cendrowska

Increasing evidence suggests that amyloid polymorphism gives rise to different strains of amyloids with distinct toxicities and pathology-spreading properties. Validating this hypothesis is challenging due to a lack of tools and methods that allow for the ...

National Academy of Sciences2020

Extent of N-terminus exposure of monomeric alpha-synuclein determines its aggregation propensity

Hilal Lashuel, Anass Chiki

As an intrinsically disordered protein, monomeric alpha-synuclein (aSyn) occupies a large conformational space. Certain conformations lead to aggregation prone and non-aggregation prone intermediates, but identifying these within the dynamic ensemble of mo ...

Nature Research2020

Development of novel methods and tools to decipher the huntingtin post-translation modifications code

Anass Chiki

Huntington's disease (HD) is a fatal genetic neurodegenerative disorder caused by a CAG repeat expansion in the Huntingtin gene of more than 36 repeats. This repeat is translated into a polyglutamine (polyQ) stretch within the first exon-encoded region of ...

EPFL2020

Phosphorylation of the overlooked tyrosine 310 regulates the structure, aggregation, and microtubule- and lipid-binding properties of Tau

Hilal Lashuel, Anass Chiki, Nadine Aït Bouziad, Galina Limorenko

The microtubule-associated protein Tau is implicated in the pathogenesis of several neurodegenerative disorders, including Alzheimer's disease. Increasing evidence suggests that post-translational modifications play critical roles in regulating Tau's norma ...

2020

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

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

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

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

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

American Society for Biochemistry and Molecular Biology Inc.2018

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

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

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

Exploring the role of post-translational modifications in regulating α-synuclein interactions by studying the effects of phosphorylation on nanobody binding

Juan Kiwi, Bruno Claude Daniel Fauvet, Hilal Lashuel, Anass Chiki, Farah El Turk

Intracellular deposits of α-synuclein in the form of Lewy bodies are major hallmarks of Parkinson’s disease (PD) and a range of related neurodegenerative disorders. Post-translational modifications (PTMs) of α-synuclein are increasingly thought to be major ...

2018

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, Annalisa Ansaloni, Francesco Simone Ruggeri, Ritwik Burai, Sophie Vieweg, Sean Michael Deguire, Urszula Beata Cendrowska

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