Publications associées à Motor Deficits upon Alpha-Synuclein Expression in the Nigrostriatal System Are Due to a Loss of Dopaminergic Vesicles and Reduced Dopamine Release at an early Stage of Neurodegeneration

Publications associées (32)

Rational Optimization of D3r/gsk-3(3 Dual Target-directed Ligands as Potential Treatment for Bipolar Disorder: Design, Synthesis, X-ray Crystallography, Molecular Dynamics Simulations, In Vitro Adme, And In Vivo Pharmacokinetic Studies

Bipolar disorder is a complex neuropsychiatric condition with a significant unmet medical need, as current treatments lack disease-modifying properties and multimodal therapeutic effects. To overcome the limitations of single-target drugs, we designed dual ...

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER2025

Assessment of neurobehavioural traits under gnotobiotic conditions: an approach for multiple analyses in the same mouse

Aleksandra Radenovic, Arielle Louise Planchette, Raphaël Doenlen

The gut-microbiota-brain axis influences neuroinflammation, neural development and behaviour such as sociability, memory and anxiety. To study these traits in vivo, especially during development or disease, it is crucial to analyse them over time and with ...

2025

Distinct ultrastructural phenotypes of glial and neuronal alpha-synuclein inclusions in multiple system atrophy

Henning Paul-Julius Stahlberg, Marta Di Fabrizio, Amanda Jennifer Lewis, Domenic Burger

Multiple System Atrophy is characterized pathologically by the accumulation of alpha-synuclein (aSyn) into glial cytoplasmic inclusions (GCIs). The mechanism underlying the formation of GCIs is not well understood. In this study, correlative light and elec ...

2024

From Sequence to Dynamics to Function: Computational Design of Allostery and Ligand Selectivity in G-Protein Coupled Receptors

Mahdi Hijazi

The phenomenon of allostery, a general property in proteins that has been heralded as "the second secret of life" remains elusive to our understanding and even more challenging to incorporate into protein design. One example of allosteric proteins with gre ...

EPFL2024

Unveiling the complexity of learning and decision-making

Wei-Hsiang Lin

Reinforcement learning (RL) is crucial for learning to adapt to new environments. In RL, the prediction error is an important component that compares the expected and actual rewards. Dopamine plays a critical role in encoding these prediction errors. In my ...

EPFL2024

Investigating the intra-molecular and inter-molecular effects of post-translational modifications on intrinsically disordered protein regions and structured protein regions

Zhidian Zhang

Post-translational modifications (PTMs) play a pivotal role in regulating protein structure, interaction, and function. Aberrant PTM patterns are associated with diseases. Moreover, individual PTMs have a complex interaction with each other, known as PTM c ...

EPFL2024

The role of LRRK2 in lung adenocarcinoma

Aspasia Gkasti

Lung cancer is the leading cause of cancer-related deaths worldwide and the most common lung cancer subtype is lung adenocarcinoma (LUAD). Frequently mutated genes involve activating mutations in KRAS and loss of function mutations in TP53. LUADs primarily ...

EPFL2024

Opportunities and challenges in design and optimization of protein function

Bruno Emanuel Ferreira De Sousa Correia, Casper Alexander Goverde

The field of protein design has made remarkable progress over the past decade. Historically, the low reliability of purely structure-based design methods limited their application, but recent strategies that combine structure-based and sequence-based calcu ...

Nature Portfolio2024

Predicting protein interactions using geometric deep learning on protein surfaces

Freyr Sverrisson

In the domain of computational structural biology, predicting protein interactions based on molecular structure remains a pivotal challenge. This thesis delves into this challenge through a series of interconnected studies. The first chapter introduces th ...

EPFL2024

Structures of the Foamy virus fusion protein reveal an unexpected link with the F protein of paramyxo- and pneumoviruses

Bruno Emanuel Ferreira De Sousa Correia, Casper Alexander Goverde

Foamy viruses (FVs) constitute a subfamily of retroviruses. Their envelope (Env) glycoprotein drives the merger of viral and cellular membranes during entry into cells. The only available structures of retroviral Envs are those from human and simian immuno ...

2024

Mechanisms and functions of protein S-acylation

Françoise Gisou van der Goot Grunberg, Laurence Gouzi Abrami, Francisco De Magalhães Sarmento Ribeiro De Mesquita

Over the past two decades, protein S-acylation (often referred to as S-palmitoylation) has emerged as an important regulator of vital signalling pathways. S-Acylation is a reversible post-translational modification that involves the attachment of a fatty a ...

Nature Portfolio2024

Microsecond Time-Resolved Cryo-Electron Microscopy

Oliver Florian Harder

Recently, single-particle cryo-electron microscopy emerged as a technique capable of determining protein structures at near-atomic resolution and resolving protein dynamics with a temporal resolution ranging from second to milliseconds. This thesis describ ...

EPFL2024

Development of tools and methods for protein identification: From single molecules to in vivo applications

Salome Riccarda Püntener

As the fundamental machinery orchestrating cellular functions, proteins influence the state of every cell profoundly. As cells exhibit significant variations from one to another, analyzing the proteome on a single-cell level is imperative to unravel their ...

EPFL2024

White adipose tissue distribution and amount are associated with increased white matter connectivity

Jean-Philippe Thiran, Gabriel Girard, Elda Fischi Gomez, Philipp Johannes Koch

Obesity represents a significant public health concern and is linked to various comorbidities and cognitive impairments. Previous research indicates that elevated body mass index (BMI) is associated with structural changes in white matter (WM). However, a ...

Wiley2024

Engineering novel protein interactions with therapeutic potential using deep learning-guided surface design

Anthony Marchand

Proteins are foundational biomolecules of life playing a crucial role in a myriad of biological processes. Their function often requires interplay with other biomolecules, including proteins themselves. Protein-protein interactions (PPIs) are essential for ...

EPFL2024

Computational drug development for membrane protein targets

Pierre Vogel, Henning Paul-Julius Stahlberg, Shuguang Yuan, Dongchun Ni, Babatunde Edukpe Ekundayo

The application of computational biology in drug development for membrane protein targets has experienced a boost from recent developments in deep learning-driven structure prediction, increased speed and resolution of structure elucidation, machine learni ...

2024

Synergetic Support of Cartilage Homeostasis via Coupled Thermal-Hydrostatic Pressure Stimuli

Yanheng Guo

Cartilage homeostasis, crucial for musculoskeletal function, is orchestrated by interconnected biophysical cues. In healthy cartilage, repetitive compressive loading not only elicits a range of mechanical stimuli but also induces a gradual transient temper ...

EPFL2024

Striatal Dopamine Signals and Reward Learning

Meriam Malekzadeh, Robin François Virginien Dard, Carl Petersen, Sylvain Crochet, Yanqi Liu, Parviz Ghaderi, Christos Sourmpis, Pol Bech Vilaseca, Mauro Pulin, Anthony Pierre Robert Renard

We are constantly bombarded by sensory information and constantly making decisions on how to act. In order to optimally adapt behavior, we must judge which sequences of sensory inputs and actions lead to successful outcomes in specific circumstances. Neuro ...

Oxford Univ Press2023

GABAergic-like dopamine synapses in the brain

Maria Reva

Dopamine synapses play a crucial role in volitional movement and reward-related behaviors, while dysfunction of dopamine synapses causes various psychiatric and neurological disorders. Despite this significance, the true biological nature of dopamine synap ...

2023

Development and validation of an expanded antibody toolset that captures alpha-synuclein pathological diversity in Lewy body diseases

Hilal Lashuel, Johannes Burtscher, Melek Firat Altay, Somanath Jagannath

The abnormal aggregation and accumulation of alpha-synuclein (aSyn) in the brain is a defining hallmark of synucleinopathies. Various aSyn conformations and post-translationally modified forms accumulate in pathological inclusions and vary in abundance amo ...

Nature Portfolio2023