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CA150 expression delays striatal cell death in overexpression and knock-in conditions for mutant huntingtin neurotoxicity

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Publications associées (40)

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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

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

Pronounced α-synuclein pathology in a seeding-based mouse model is not sufficient to induce mitochondrial respiration deficits in the striatum and amygdala

Jean-Christophe Copin, Maria del Carmen Sandi Perez, Hilal Lashuel, Johannes Burtscher

Increasing evidence suggests that crosstalk between α-synuclein pathology formation and mitochondrial dysfunction plays a central role in the pathogenesis of Parkinson’s disease and related synucleinopathies. While mitochondrial dysfunction is a well-studi ...

2020

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

Glutaredoxin 1 Downregulation in the Substantia Nigra Leads to Dopaminergic Degeneration in Mice

Bernard Schneider

Background Parkinson's disease (PD) is characterized by a severe loss of the dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc). Perturbation of protein thiol redox homeostasis has been shown to play a role in the dysregulation of cell ...

2020

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

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

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

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

Amplified engagement of prefrontal cortex during control of voluntary action in Tourette syndrome

Sophie Jacqueline Andrée Betka

Tourette syndrome is characterized by 'unvoluntary' tics, which are compulsive, yet often temporarily suppressible. The inferior frontal gyms is implicated in motor control, including inhibition of pre-potent actions through influences on downstream subcor ...

OXFORD UNIV PRESS2020

The role of OCT4 and SOX2 in regulating chromatin accessibility and cell fate across the cell cycle in embryonic stem cells

Torgil Elias Friman

Precise spatiotemporal regulation of gene expression is essential for development and homeostasis of complex organisms. This is achieved in large part by sequence-specific transcription factors (TF) that bind to genomic regulatory elements to activate or r ...

EPFL2019

A Computational Model of Loss of Dopaminergic Cells in Parkinson's Disease Due to Glutamate-Induced Excitotoxicity

Srikanth Ramaswamy, Vignayanandam Ravindernath Muddapu

Parkinson's disease (PD) is a neurodegenerative disease associated with progressive and inexorable loss of dopaminergic cells in Substantia Nigra pars compacta (SNc). Although many mechanisms have been suggested, a decisive root cause of this cell loss is ...

2019

Mechanistic insights into AMP-activated protein kinase-dependent gene expression

Caterina Collodet

AMP-activated protein kinase (AMPK) is a fundamental enzyme that controls energy homeostasis, through orchestrating the cellular response to a reduction in energy availability. Under conditions of cellular energy stress AMPK senses the decrease in ATP leve ...

EPFL2019

eNAMPT actions through nucleus accumbens NAD + /SIRT1 link increased adiposity with sociability deficits programmed by peripuberty stress

Johan Auwerx, Maria del Carmen Sandi Perez, Olivia Zanoletti, João Pedro de Matos Rodrigues, Simone Astori, Jocelin Grosse, Marie-Isabelle Guillot de Suduiraut, Ioannis Zalachoras, Laia Morato Fornaguera, Sriparna Ghosal

Obesity is frequently associated with impairments in the social domain, and stress at puberty can lead to long-lasting changes in visceral fat deposition and in social behaviors. However, whether stress-induced changes in adipose tissue can affect fat-to-b ...

2022

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

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

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

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

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

Two-photon calcium imaging of neocortical projection neurons in whisker somatosensory cortex during goal-directed sensorimotor learning

Dimitra Angeliki Vavladeli

Excitatory projection neurons of the neocortex are thought to play important roles in perceptual and cognitive functions of the brain by directly connecting diverse cortical and subcortical areas. However, many aspects of the anatomical and functional orga ...

EPFL2018

Single live cell monitoring of protein turnover reveals intercellular variability and cell cycle dependence of degradation rates

Andrea Brigitta Alber

Cells need to be able to precisely control their proteome composition in order to maintain homeostasis. This is of particular relevance in fast dividing cells, such as embryonic stem cells, since their global protein levels need to be doubled at each divis ...

EPFL2018

Comprehensive analysis of the circadian nuclear and cytoplasmic transcriptome in mouse liver

Felix Naef, Cédric Gobet, Benjamin Dieter Weger, Clémence Yumie Syloun Hurni

In eukaryotes, RNA is synthesised in the nucleus, spliced, and exported to the cytoplasm where it is translated and finally degraded. Any of these steps could be subject to temporal regulation during the circadian cycle, resulting in daily fluctuations of ...

PUBLIC LIBRARY SCIENCE2022

Layer, cell-type and pathway-specific thalamocortical input to mouse somatosensory cortex

Berat Semihcan Sermet

In the mouse whisker system, sensory information is relayed to the whisker somatosensory cortex by two major thalamic nuclei, the ventral posterior medial nucleus (VPM) and the posterior medial nucleus (POM). While the cortical axonal innervation pattern o ...

EPFL2018

Er-Phagy: Mechanisms, Regulation, And Diseases Connected To The Lysosomal Clearance Of The Endoplasmic Reticulum

Maurizio Molinari

ER-phagy (reticulophagy) defines the degradation of portions of the endoplasmic reticulum (ER) within lysosomes or vacuoles. It is part of the self-digestion (i.e., autophagic) programs recycling cytoplasmic material and organelles, which rapidly mobilize ...

2022