Publications related to HDAC4 Reduction: A Novel Therapeutic Strategy to Target Cytoplasmic Huntingtin and Ameliorate Neurodegeneration

Anti-miR-873-5p improves alcohol-related liver disease by enhancing hepatic deacetylation via SIRT1

Background & Aims: Current therapies for the treatment of alcohol-related liver disease (ALD) have proven largely ineffective. Patients relapse and the disease progresses even after liver transplantation. Altered epigenetic mechanisms are characteristic of ...

Elsevier2024

Substrates and Cyclic Peptide Inhibitors of the Oligonucleotide-Activated Sirtuin 7

Alexander Lund Nielsen

The sirtuins are NAD+-dependent lysine deacylases, comprising seven isoforms (SIRT1-7) in humans, which are involved in the regulation of a plethora of biological processes, including gene expression and metabolism. The sirtuins share a common hydrolytic m ...

Wiley-VCH Verlag GmbH2023

Early motor skill acquisition in healthy older adults: brain correlates of the learning process

Manon Chloé Durand-Ruel, Pablo Maceira Elvira, Friedhelm Christoph Hummel, Takuya Morishita, Maeva Moyne, Chang-Hyun Park

Motor skill learning is a crucial process at all ages. However, healthy aging is often accompanied by a reduction in motor learning capabilities. This study characterized the brain dynamics of healthy older adults during motor skill acquisition and identif ...

OXFORD UNIV PRESS INC2023

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

Neuronal correlates of goal-directed sensorimotor transformation in sensory, motor and higher-order cortical areas

Anastasiia Oryshchuk

An important function of the brain is to interpret incoming sensory information from the outside world to guide adaptive behavior. Understanding how and where sensory information is transformed into motor commands in a context- and learning-dependent manne ...

EPFL2023

Brain connectome correlates of short-term motor learning in healthy older subjects

Manon Chloé Durand-Ruel, Friedhelm Christoph Hummel, Takuya Morishita, Maeva Moyne, Chang-Hyun Park

The motor learning process entails plastic changes in the brain, especially in brain network reconfigurations. In the current study, we sought to characterize motor learning by determining changes in the coupling behaviour between the brain functional and ...

Elsevier Masson, Corp Off2023

Investigating the neuromechanical control of healthy gait modulation and pathological gaits observed in cerebral palsy using neuromuscular simulations

Andrea Di Russo

Locomotion is based on a sophisticated interaction among the environment, the musculoskeletal system, the spinal cord, and the brain locomotor areas. Quality of life is strongly related to the proper capability of this movement. However, many pathologies, ...

EPFL2023

Mechanisms underlying reinforcement learning of motor skills

Pierre Theopistos Vassiliadis

Motor learning allows animals, including human beings, to acquire skills that are es-sential for efficient interactions with the environment. This ability to learn new motor skills is of great practical relevance for daily-life activities (such as when lea ...

EPFL2023

Epigenetic memory aids: Synaptic and molecular effects of HDAC inhibition that support memory formation

Allison Marie Burns

Learning and memory rely on synaptic communication in which intracellular signals are transported to the nucleus to stimulate transcriptional activation. Memory induced transcriptional increases are accompanied by alterations to the epigenetic landscape an ...

EPFL2022

Class I histone deacetylases (HDAC1-3) are histone lysine delactylases

Di Zhang, Alexander Lund Nielsen, Carlos Moreno Yruela

Lysine L-lactylation [K(L-la)] is a newly discovered histone mark stimulated under conditions of high glycolysis, such as the Warburg effect. K(L-la) is associated with functions that are different from the widely studied histone acetylation. While K(L-la) ...

2022

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

Nathan Alain Denis Riguet

Despite the fact that the gene responsible for Huntington's disease (HD) is known, we still do not understand the underlying mechanisms leading to neurodegeneration and death. Identifying and understanding the mechanisms controlling mutant huntingtin (mHtt ...

EPFL2022

Does one size fit all? - Towards the optimization and personalization of non-invasive brain stimulation paradigms to enhance motor learning

Laurijn Rianne Draaisma

The acquisition and re-acquisition of motor skills is an important aspect of daily life and in the recovery after a stroke. Non-invasive brain stimulation (NIBS) is a technique that is used to improve motor learning and enhance motor recovery in stroke sur ...

EPFL2022

Early motor skill acquisition in healthy older adults: functional MRI and connectome correlates

Manon Chloé Durand-Ruel

decrement have been proposed, such as weakened acquisition of the motor skill. While the processes at play during the initial acquisition phase have been well-characterized in young adults, they were only scarcely investigated in older adults. The goal of ...

EPFL2022

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

Hilal Lashuel, Lorène Aeschbach, Nathan Alain Denis Riguet

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

Epigenetic plasticity as a signature for memory allocation

Giulia Santoni

Long-lasting memories are stored in a small set of neurons scattered throughout the brain, so-called engram cells. To define a stable engram each region of the brain involved in memory storage recruits between 5 and 20 percent of excitatory neurons. In par ...

EPFL2022

Opportunities and challenges of alpha-synuclein as a potential biomarker for Parkinson's disease and other synucleinopathies

Hilal Lashuel, Pedro José Santana Ribeiro Magalhães

Parkinson's disease (PD), the second most common progressive neurodegenerative disease, develops and progresses for 10-15 years before the clinical diagnostic symptoms of the disease are manifested. Furthermore, several aspects of PD pathology overlap with ...

NATURE PORTFOLIO2022

Alpha-synuclein as a Potential Biomarker for Parkinson’s Disease and Other Synucleinopathies: Gaps, Challenges, and Opportunities

Hilal Lashuel, Pedro José Santana Ribeiro Magalhães

Parkinson's disease (PD), the second most common progressive neurodegenerative disease, develops and progresses for 10-15 years before the clinical diagnostic symptoms of the disease are manifested. Furthermore, several aspects of PD pathology overlap with ...

2022

Reward timing matters in motor learning

Pierre Theopistos Vassiliadis, Julie Duqué

Reward timing, that is, the delay after which reward is delivered following an action is known to strongly influence reinforcement learning. Here, we asked if reward timing could also modulate how people learn and consolidate new motor skills. In 60 health ...

CELL PRESS2022

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

SIRT7 modulates the stability and activity of the renal K-Cl cotransporter KCC4 through deacetylation

Olivier Staub, Johan Auwerx, Lilia Noriega Lopez, Dongryeol Ryu

SIRT7 is a NAD(+)-dependent deacetylase that controls important aspects of metabolism, cancer, and bone formation. However, the molecular targets and functions of SIRT7 in the kidney are currently unknown. In silico analysis of kidney transcripts of the BX ...

2021