Publications related to An integrative approach to elucidate the mechanisms and dynamics of Huntingtin aggregation and inclusion formation in neuronal models of Huntington's Disease

Related publications (34)

Ultrastructural characterization of tau pathology in the human post‐mortem Alzheimer’s disease brain

Louis Travers, Philippine Laure Diane Schneider, Eglantine Vialaneix, Henning Paul-Julius Stahlberg, Amanda Jennifer Lewis

Neuropathological tau tangles in Alzerheimer’s disease (AD) have been roughly characterized into pre‐tangles, mature tangles and ghost tangles. However, to date, their maturation in the human brain is poorly understood. Here, we aimed to define the structu ...

Wiley2024

Exploring the therapeutic potential of Huntingtin native state stabilization through targeting its interacting partners

Enzo Sébastien Benjamin Morro

Huntington's disease (HD) is a devastating neurodegenerative disorder marked by the accumulation of Huntingtin protein (HTT) fragments in HD neuronal cells. These aggregates are predominantly composed of polyglutamine (polyQ)-containing HTT N-terminal frag ...

EPFL2024

Meeting our Makers: Uncovering the cis-regulatory activity of transposable elements using statistical learning

Cyril David Son-Tuyên Pulver

The adaptation of organisms to their environment depends on the innovative potential inherent to genetic variation. In complex organisms such as mammals, processes like development and immunity require tight gene regulation. Complex forms emerge more often ...

EPFL2024

Targeting TDP-43 Proteinopathies in Neurodegeneration by its Native-State Stabilization

Lixin Yang

Preventing the misfolding or aggregation of TDP-43 is the most actively pursued disease-modifying strategy to treat amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. In our work, we provide proof of concept that native state stabili ...

EPFL2024

Hydrophobic Interaction and its Small Molecule effect

Ting Mao

Protein stabilization has a crucial rule sustaining biological functionality, disease prevention, and pharmaceutical formulation stabilization, and yet its stabilization mechanism by small molecules such as amino acids is not fully understood. In this work ...

EPFL2024

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

Digital reconstruction of the mammalian spinal cord: from anatomical reference volume to cell type atlas of the mouse spinal cord

Ihor Kuras

The spinal cord is an elongated nervous structure that together with the brain forms the central nervous system. It relays sensory and motor information between the brain and the body, thus controlling most somatic and autonomic body functions. In recent y ...

EPFL2023

From event-based surprise to lifelong learning. A journey in the timescales of adaptation

Martin Louis Lucien Rémy Barry

Humans and animals constantly adapt to their environment over the course of their life. This thesis seeks to integrate various timescales of adaptation, ranging from the adaptation of synaptic connections between spiking neurons (milliseconds), rapid behav ...

EPFL2023

Transposable elements contribute to the spatiotemporal microRNA landscape in human brain development

Didier Trono, Evaristo Jose Planet Letschert, Shaoline Sheppard, Christopher James Playfoot

Transposable elements (TEs) contribute to the evolution of gene regulatory networks and are dynamically expressed throughout human brain development and disease. One gene regulatory mechanism influenced by TEs is the miRNA system of post-transcriptional co ...

2022

Modeling, analysis, and design of complex biological networks

Mohammadomid Oftadeh

Automating experimental procedures has resulted in an unprecedented increase in the volume of generated data, which, in turn, has caused an accumulation of unprocessed data. As a result, the need to develop tools to analyze data systematically has been ris ...

EPFL2023

Loss of Motor Cortical Inputs to the Red Nucleus after CNS Disorders in Nonhuman Primates

Simon Borgognon

The premotor (PM) and primary motor (M1) cortical areas broadcast voluntary motor commands through multiple neuronal pathways, including the corticorubral projection that reaches the red nucleus (RN). However, the respective contribution of M1 and PM to co ...

SOC NEUROSCIENCE2023

Diverse cell-specific patterns of alternative polyadenylation in Drosophila

Bart Deplancke

Most genes in higher eukaryotes express isoforms with distinct 3' untranslated regions (3' UTRs), generated by alternative polyadenylation (APA). Since 3' UTRs are predominant locations of post-transcriptional regulation, APA can render such programs condi ...

Nature Portfolio2022

Fast-Spiking Interneurons of the Premotor Cortex Contribute to Initiation and Execution of Spontaneous Actions

Silvestro Micera

Planning and execution of voluntary movement depend on the contribution of distinct classes of neurons in primary motor and premotor areas. However, timing and pattern of activation of GABAergic cells during specific motor behaviors remain only partly unde ...

SOC NEUROSCIENCE2023

Current challenges in understanding the role of enhancers in disease

Bart Deplancke

Enhancers play a central role in the spatiotemporal control of gene expression and tend to work in a cell-type-specific manner. In addition, they are suggested to be major contributors to phenotypic variation, evolution and disease. There is growing eviden ...

Nature Research2022

Aging Fly Cell Atlas identifies exhaustive aging features at cellular resolution

Maria Brbic

Aging is characterized by a decline in tissue function, but the underlying changes at cellular resolution across the organism remain unclear. Here, we present the Aging Fly Cell Atlas, a single-nucleus transcriptomic map of the whole aging Drosophila. We c ...

American Association for the Advancement of Science2023

A New Chemoenzymatic Semisynthetic Approach Provides Insight into the Role of Phosphorylation beyond Exon1 of Huntingtin and Reveals N-Terminal Fragment Length-Dependent Distinct Mechanisms of Aggregation

Hilal Lashuel, Rajasekhar Kolla, Jonathan Jean-Pierre Ricci, Andreas Reif, Gopinath Pushparathinam

Huntington’s disease is a neurodegenerative dis- order caused by the expansion of a polyglutamine repeat (>36Q) in the N-terminal domain of the huntingtin protein (Htt), which renders the protein or fragments thereof more prone to aggregate and form inclus ...

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, 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

Towards elucidating the structural and cellular determinants of a-synuclein seeding and toxicity

Somanath Jagannath

Although it has been nearly two and half decades since the discovery of alpha-synuclein (aSyn) as the major component of Lewy bodies (LBs), our understanding of the involvement of different aSyn species, their seeding, spreading and toxicity in Parkinson's ...

EPFL2022

Enhancing mitochondrial quality control to fight neuromuscular degeneration in aging and disease

Mario Romani

Loss of mitochondrial function and proteostasis typify aging and age-associated degenerative disorders such as Alzheimer's disease and muscle aging. To date, no cure or preventive measure is available to manage these conditions. Alterations of cellular pro ...

EPFL2021

N-terminal mutant huntingtin deposition correlates with CAG repeat length and symptom onset, but not neuronal loss in Huntington's disease

Hilal Lashuel, Nathan Alain Denis Riguet, Lorène Aeschbach

Huntington's disease (HD) is caused by a CAG repeat expansion mutation in the gene encoding the huntingtin (Htt) protein, with mutant Htt protein subsequently forming aggregates within the brain. Mutant Htt is a current target for novel therapeutic strateg ...

ACADEMIC PRESS INC ELSEVIER SCIENCE2022