A5051117101- Amyotrophic Lateral Sclerosis Research
- Autophagy in Disease and Therapy
- Zebrafish Biomedical Research Applications
- Neurogenetic and Muscular Disorders Research
- Genetic Neurodegenerative Diseases
- Muscle and Compartmental Disorders
- Parkinson's Disease Mechanisms and Treatments
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Prion Diseases and Protein Misfolding
- Calpain Protease Function and Regulation
- CRISPR and Genetic Engineering
- Lipid metabolism and biosynthesis
- Muscle Physiology and Disorders
- Cardiovascular Function and Risk Factors
- Nerve injury and regeneration
- MicroRNA in disease regulation
- Cholinesterase and Neurodegenerative Diseases
- Metabolism and Genetic Disorders
- Neural dynamics and brain function
- Muscle metabolism and nutrition
- Neuroscience and Neuropharmacology Research
- Hereditary Neurological Disorders
Inserm
2014-2025
Université Paris Cité
2018-2025
Institut des Maladies Génétiques Imagine
2021-2025
Institut Necker Enfants Malades
2018-2024
Centre National de la Recherche Scientifique
2023-2024
Assistance Publique – Hôpitaux de Paris
2023-2024
Hôpital Necker-Enfants Malades
2023
Sorbonne Université
2014-2021
Institut du Cerveau
2021
International Council on Mining and Metals
2014
Abstract Amyotrophic lateral sclerosis (ALS) has substantial heritability, in part shared with fronto-temporal dementia (FTD). We show that ALS heritability is enriched splicing variants and binding sites of 6 RNA-binding proteins including TDP-43 FUS. A transcriptome wide association study (TWAS) identified loci associated ALS, NUP50 encoding for the nucleopore basket protein NUP50. Independently, rare were risk ( P = 3.71.10 −03 ; odds ratio 3.29; 95%CI, 1.37 to 7.87) a cohort 9,390...
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 Pathogenic mutations within the TBK1 gene leading to haploinsufficiency are causative of amyotrophic lateral sclerosis (ALS). This is linked autophagy and inflammation, two cellular mechanisms reported be dysregulated in ALS patients, although its functional role pathogenesis could involve other players. We targeted ortholog zebrafish, an optimal vertebrate model for investigating genetic defects neurological disorders. generated zebrafish models with invalidating tbk1 using...
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...
Lipin-1 deficiency is a life-threatening disease that causes severe rhabdomyolysis (RM) and chronic symptoms associated with oxidative stress. In the absence of treatment, Hydroxychloroquine sulfate (HCQ) was administered to patients off label use on compassionate basis in order improve their physical conditions.Eleven LPIN1 mutations were treated HCQ. Clinical biological efficacy tolerance assessed, including pain quality life, capacities, cardiopulmonary parameters, creatine kinase levels...
The GGGGCC hexanucleotide repeat expansion (HRE) of the
Abstract Patients with fatty acid oxidation disorders (FAODs) experience muscle symptoms due to impaired ATP metabolism and the toxicity of accumulated mitochondrial FAO substrates or intermediates, especially during catabolic states. A major issue is absence specific sensible biomarkers evaluate metabolic equilibrium. The relationship between cardiac output (Q) oxygen consumption (VO 2 ) incremental exercise (dQ/dVO provides an indirect surrogate function. high dQ/dVO slope indicates...
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...
Abstract The genetic basis of amyotrophic lateral sclerosis (ALS) is still incompletely understood. Using two independent strategies, we show here that a large part ALS heritability lies in genes expressed inhibitory and excitatory neurons, especially at splicing sites regulated by defined set RNA binding proteins including TDP-43 FUS. We conducted transcriptome wide association study (TWAS) identified 59 loci associated with ALS, 14 previously genes, some them not reaching significance...
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...
ABSTRACT Myotonic dystrophy type 1 (DM1) is a multisystemic neuromuscular disease characterized by CTG repeat expansion in the 3’ untranslated region of gene coding for dystrophia myotonica protein kinase (DMPK). Presence expanded repeats DMPK-mRNAs leads to sequestration RNA binding factors such as Muscleblind like (MBNL) proteins resulting widespread splicing defects contributing progressive muscle weakness and myotonia. Here, we show that abnormal SORBS1 exon 25 found skeletal myotonic...
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...
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...