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

Publications associées (32)

Rational combination platform trial design for children and young adults with Diffuse Midline Glioma: a report from PNOC

Diffuse midline glioma (DMG) is a devastating pediatric brain tumor unresponsive to hundreds of clinical trials. Approximately 80% of DMGs harbor H3K27M oncohistones, which reprogram the epigenome to increase the metabolic profile of the tumor cells. We ha ...

2023

Mitochondrial matrix protein LETMD1 maintains thermogenic capacity of brown adipose tissue in male mice

Johan Auwerx, Maroun Bou Sleiman, Jun Yong Kim, Xiaoxu Li

Brown adipose tissue (BAT) has abundant mitochondria with the unique capability of generating heat via uncoupled respiration. Here, Park et al. identify LETMD1 as a mitochondrial matrix protein enriched in brown adipose tissue (BAT) and reveal a crucial ro ...

Nature Portfolio2023

SLC25A46 promotes mitochondrial fission and mediates resistance to lipotoxic stress in INS-1E insulin-secreting cells

Loïc Dayon, Andreas Wiederkehr

Glucose sensing in pancreatic D-cells depends on oxidative phosphorylation and mitochondria-derived signals that promote insulin secretion. Using mass spectrometry-based phosphoproteo-mics to search for downstream effectors of glucose-dependent signal tran ...

COMPANY BIOLOGISTS LTD2023

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

Axonal projections from mouse whisker-related sensory cortex

Yanqi Liu

Neurons primarily communicate through release of neurotransmitter from presynaptic specialisations along their axonal arborisations. In order to understand the functional role of a specific neuron, it is therefore of great interest to know the structure of ...

EPFL2023

Transcriptomic analysis reveals mitochondrial pathways associated with distinct adolescent behavioral phenotypes and stress response

Maria del Carmen Sandi Perez, Dogukan Hazar Ülgen

Adolescent individuals exhibit great variability in cortical dynamics and behavioral outcomes. The developing adolescent brain is highly sensitive to social experiences and environmental insults, influencing how personality traits emerge. A distinct patter ...

2023

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

Role of the cystathionine beta-synthase / H2S pathway in the development of cellular metabolic dysfunction and pseudohypoxia in down syndrome

Theodora Panagaki

Background: Overexpression of the transsulfuration enzyme cystathionine-beta-synthase (CBS), and overproduction of its product, hydrogen sulfide (H2S) are recognized as potential pathogenetic factors in Down syndrome (DS). The purpose of the study was to d ...

ELSEVIER2022

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

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

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, Ahmed Sherif Saad Zaghloul Mohamed Sadek, 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

Pum2 and TDP-43 refine area-specific cytoarchitecture post-mitotically and modulate translation of Sox5, Bcl11b, and Rorb mRNAs in developing mouse neocortex

Nagammal Neelagandan

In the neocortex, functionally distinct areas process specific types of information. Area identity is established by morphogens and transcriptional master regulators, but downstream mechanisms driving area-specific neuronal specification remain unclear. He ...

eLIFE SCIENCES PUBL LTD2022

Robust designation of meiotic crossover sites by CDK-2 through phosphorylation of the MutS gamma complex

Alexander Woglar

Crossover formation is essential for proper segregation of homologous chromosomes during meiosis. Here, we show that Caenorhabditis elegans cyclin-dependent kinase 2 (CDK-2) partners with cyclin-like protein COSA-1 to promote crossover formation by promoti ...

National Academy of Sciences2022

Data-driven whole mouse brain modeling for multi-scale simulations

Dimitri Bruno Marie Rodarie

In this thesis, we present a data-driven iterative pipeline to generate, simulate and validate point-neuron models of the whole mouse brain. The ultimate goal is to replicate close loop experiments with a virtual body in a virtual world. This pipeline was ...

EPFL2022

Regulation of Src tumor activity by its N-terminal intrinsically disordered region

Florence Armand, Romain Hamelin

The membrane-anchored Src tyrosine kinase is involved in numerous pathways and its deregulation is involved in human cancer. Our knowledge on Src regulation relies on crystallography, which revealed intramolecular interactions to control active Src conform ...

SPRINGERNATURE2022

Axonal and Dendritic Morphology of Excitatory Neurons in Layer 2/3 Mouse Barrel Cortex Imaged Through Whole-Brain Two-Photon Tomography and Registered to a Digital Brain Atlas

Carl Petersen, Sylvain Crochet, Georgios Foustoukos, Yanqi Liu

Communication between cortical areas contributes importantly to sensory perception and cognition. On the millisecond time scale, information is signaled from one brain area to another by action potentials propagating across long-range axonal arborizations. ...

FRONTIERS MEDIA SA2022

Emerging principles of spacetime in brains: Meeting report on spatial neurodynamics

Carl Petersen

How do neurons and networks of neurons interact spatially? Here, we overview recent discoveries revealing how spatial dynamics of spiking and postsynaptic activity efficiently expose and explain fundamental brain and brainstem mechanisms behind detection, ...

CELL PRESS2022

The Neuron Phenotype Ontology: A FAIR Approach to Proposing and Classifying Neuronal Types

Sean Lewis Hill, Mohameth François Sy

The challenge of defining and cataloging the building blocks of the brain requires a standardized approach to naming neurons and organizing knowledge about their properties. The US Brain Initiative Cell Census Network, Human Cell Atlas, Blue Brain Project, ...

HUMANA PRESS INC2022

Computational Studies of the Proton-Coupled Metal Ion Transport in the SLC11/NRAMP Family of Transporters

Maria Letizia Merlini

In the last years, it has been demonstrated a link between the overload of metal ions inside nervous system cells and the onset of severe neurodegenerative diseases. This prompted the investigation of the structural and functional properties of transporter ...

EPFL2022

Disruption of layer-specific visual processing in a model of focal neocortical epilepsy

Silvestro Micera

The epileptic brain is the result of a sequence of events transforming normal neuronal populations into hyperexcitable networks supporting recurrent seizure generation. These modifications are known to induce fundamental alterations of circuit function and ...

OXFORD UNIV PRESS INC2022