A5031745517- Amyotrophic Lateral Sclerosis Research
- Zebrafish Biomedical Research Applications
- Neurogenetic and Muscular Disorders Research
- Cholinesterase and Neurodegenerative Diseases
- Autophagy in Disease and Therapy
- Parkinson's Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Neurological Disease Mechanisms and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Ion channel regulation and function
- Alzheimer's disease research and treatments
- Neurological diseases and metabolism
- Obsessive-Compulsive Spectrum Disorders
- Trypanosoma species research and implications
- Epilepsy research and treatment
- Neonatal and fetal brain pathology
- CRISPR and Genetic Engineering
- Autism Spectrum Disorder Research
- RNA regulation and disease
- Retinal and Optic Conditions
- Genetics and Neurodevelopmental Disorders
- Cell Adhesion Molecules Research
- Neurological Disorders and Treatments
- Genetics, Aging, and Longevity in Model Organisms
- Pluripotent Stem Cells Research
Université Paris Cité
2015-2024
Inserm
2013-2024
Sorbonne Université
2013-2024
Institut des Maladies Génétiques Imagine
2021-2024
Sorbonne Paris Cité
2015-2024
Institut du Cerveau
2013-2021
Allen Institute for Brain Science
2021
Centre National de la Recherche Scientifique
2013-2019
Institut Necker Enfants Malades
2018
International Council on Mining and Metals
2014
To define the role that repeat expansions of a GGGGCC hexanucleotide sequence C9orf72 gene play in pathogenesis amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). A genetic model for ALS was developed to determine whether loss function zebrafish orthologue (zC9orf72) leads abnormalities neuronal development.C9orf72 mRNA levels were quantified brain lymphoblasts derived from FTLD ALS/FTLD patients zebrafish. Knockdown zC9orf72 performed using 2 specific...
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing, fatal disorder with no effective treatment. We used simple genetic models of ALS to screen phenotypically for potential therapeutic compounds. screened libraries compounds in C. elegans, validated hits zebrafish, and tested the most potent molecule mice small clinical trial. identified class neuroleptics that restored motility elegans was pimozide, which blocked T-type Ca2+ channels these stabilized neuromuscular transmission...
The DNA/RNA-binding proteins TDP-43 and FUS are found in protein aggregates a growing number of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) related dementia, but little is known about the neurotoxic mechanisms. We have generated Caenorhabditis elegans zebrafish animal models expressing mutant human (A315T or G348C) (S57Δ R521H) that reflect certain aspects ALS motor neuron degeneration, axonal deficits, progressive paralysis. To explore potential our humanized...
Mutations in SQSTM1, encoding for the protein SQSTM1/p62, have been recently reported 1–3.5% of patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration (ALS/FTLD). Inclusions positive SQSTM1/p62 detected neurodegenerative disorders, including ALS/FTLD. In order to investigate pathogenic mechanisms induced by SQSTM1 mutations ALS/FTLD, we developed a zebrafish model. Knock-down sqstm1 ortholog, as well impairment its splicing, led specific phenotype, consisting...
Abstract Objective DEPDC 5 was identified as a major genetic cause of focal epilepsy with deleterious mutations found in wide range inherited forms epilepsy, associated malformation cortical development certain cases. Identification frameshift, truncation, and deletion implicates haploinsufficiency the etiology epilepsy. is component GATOR 1 complex, acting negative regulator mTOR signaling. Methods Zebrafish represents vertebrate model suitable for analysis drug screening epilepsy‐related...
The most common genetic cause for amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD) is repeat expansion of a hexanucleotide sequence (GGGGCC) within the C9orf72 genomic sequence. To elucidate functional role in disease pathogenesis, we identified certain molecular interactors this factor. We determined that exists complex with SMCR8 WDR41 acts as GDP/GTP exchange factor RAB8 RAB39, 2 RAB GTPases involved macroautophagy/autophagy. Consequently, depletion neuronal cultures...
Abstract Focal cortical dysplasia, hemimegalencephaly and tubers are paediatric epileptogenic malformations of development (MCDs) frequently pharmacoresistant mostly treated surgically by the resection epileptic cortex. Availability samples has allowed significant mechanistic discoveries directly from human material. Causal brain somatic or germline mutations in AKT/PI3K/DEPDC5/MTOR genes have been identified. GABAA-mediated paradoxical depolarization, related to altered chloride (Cl−)...
The “distal axonopathy” hypothesis in amyotrophic lateral sclerosis (ALS) proposes that pathological changes occur at the neuromuscular junction (NMJ) early disease. While acetylcholinesterase (AChE) plays an important role functionality of NMJ, its potential ALS remains unexplored. Here, we identified AChE as a limiting factor regulating muscle/motor neuron connection vertebrate model ALS. Knockdown TAR DNA-binding protein 43 (TDP-43) orthologue zebrafish resulted defects motor functions...
Genes involved in Tourette syndrome (TS) remain largely unknown. We aimed to identify genetic factors contributing TS a French cohort of 120 individuals using combination hypothesis-driven and exome-sequencing approaches.We first sequenced exons SLITRK1-6 HDC the subsequently exome 12 harboring rare variants these genes find additional disorder under hypothesis oligogenic inheritance. further screened three candidate (OPRK1, PCDH10, NTSR2) preferentially expressed basal ganglia, neurotensin...
Collagen VI (COLVI), a protein ubiquitously expressed in connective tissues, is crucial for structural integrity, cellular adhesion, migration and survival. Six different genes are recognized mammalians, encoding six COLVI-chains that assemble as two 'short' (α1, α2) one 'long' chain (theoretically any of α3-6). In humans, defects the most widely heterotrimer (α123), due to mutations COL6A1-3 genes, cause heterogeneous group neuromuscular disorders, collectively termed COLVI-related muscle...
<strong>Background:</strong> Genes involved in Tourette syndrome (TS) remain largely unknown. We aimed to identify genetic factors contributing TS a French cohort of 120 individuals using combination hypothesis-driven and exome-sequencing approaches. <strong>Methods:</strong> first sequenced exons <em>SLITRK1-6</em> <em>HDC</em> the subsequently exome 12 harboring rare variants these genes find additional disorder under hypothesis oligogenic inheritance. further screened three candidate...
It has been known for a long time that epileptic seizures provoke brain neuroinflammation involving the activation of microglial cells. However, role these cells in this disease context and consequences their inflammatory on subsequent neuron network activity remain poorly understood so far. To fill gap knowledge gain better understanding microglia pathophysiology epilepsy, we used an established zebrafish Dravet syndrome epilepsy model based Scn1Lab sodium channel loss-of-function, combined...
Patients with pathogenic variants in the TANGO2 gene suffer from severe and recurrent rhabdomyolysis episodes precipitated by fasting. Autophagy functioning was analyzed vitro, primary skeletal myoblasts patients, basal fasting conditions, mutations were associated reduced LC3-II levels upon starvation. In zebrafish larvae, tango2 inhibition induced locomotor defects which exacerbated exposure to atorvastatin, a compound known cause rhabdomyolysis. Importantly, features of knockdown...
Epilepsy represents one of the most common neurological disorders, affecting an estimated 50 million people worldwide. Recent advances in genetic research have uncovered a large spectrum genes implicated various forms epilepsy, highlighting heterogeneous nature this disorder. Appropriate animal models are essential for investigating pathological mechanisms triggered by mutations epilepsy and developing specialized, targeted therapies. In recent years, zebrafish has emerged as valuable...
Dysregulated RNA metabolism caused by SMN deficiency leads to motor neuron disease spinal muscular atrophy (SMA). Current therapies improve patient outcomes but achieve no definite cure, prompting renewed efforts better understand mechanisms. The calcium channel blocker flunarizine improves function in
Abstract Organ-to-organ dissemination of viruses is a critical feature host-virus interactions. In particular, neuroinvasive are able to enter the central nervous systems (CNS), which may result in death or permanent neurological impairment. The complex mechanisms underpinning this spread poorly understood, as they depend on variety parameters, including initial site entry, route access CNS, and immune responses. To better understand these phenomena, we analyzed spatial dynamics Sindbis...
ABSTRACT KEY POINTS kcnb1 is expressed in distinct cell subtypes and various regions of the central nervous system zebrafish Brain anatomy neuronal circuits are not disrupted loss-of-function model Loss leads to altered behavior phenotype, light sound-induced locomotor impairments knock-out exhibit increased sensitivity PTZ elevated expression epileptogenesis-related genes -/- larvae show spontaneous provoked epileptiform-like electrographic activity associated with GABA regulation Objective...
Abstract Patients with pathogenic variants in the TANGO2 gene suffer from severe and recurrent rhabdomyolysis (RM) episodes precipitated by fasting. Since starvation promotes autophagy induction, we wondered whether TANGO2-related muscle symptoms result insufficiency to meet cellular demands stress conditions. Autophagy functioning was analyzed vitro , primary skeletal cells patients basal fasting In addition, developed a tango2 morphant zebrafish model assess effect of knockdown (KD) on...
Research in Epilepsy relies strongly on animal models, either for describing genetic conditions involved the disease or testing potential drugs that might alleviate symptoms [1]. In this study, we looked at differential effect of Pentylenetetrazole (PTZ), a well-known epileptogenic drug [2], 5-6 dpf zebrafish larvae two different conditions: mutant line, where gene known to be focal epilepsy was specifically knocked down, as well control mismatch oligonucleotide-injected zebrafish. The...