A5073616887- Cystic Fibrosis Research Advances
- Neonatal Respiratory Health Research
- French Urban and Social Studies
- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Cellular transport and secretion
- Neurogenesis and neuroplasticity mechanisms
- Hemoglobin structure and function
- Ion channel regulation and function
- Genetics and Neurodevelopmental Disorders
- Respiratory viral infections research
- Asthma and respiratory diseases
- Business Strategy and Innovation
- Mitochondrial Function and Pathology
- Tracheal and airway disorders
- Cultural Industries and Urban Development
- Autoimmune Neurological Disorders and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Epilepsy research and treatment
- Parkinson's Disease Mechanisms and Treatments
- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Ultrasound and Hyperthermia Applications
- Advanced biosensing and bioanalysis techniques
- Multiple Sclerosis Research Studies
Institut du Cerveau
2016-2024
Centre National de la Recherche Scientifique
2015-2023
Assistance Publique – Hôpitaux de Paris
2022-2023
Pitié-Salpêtrière Hospital
2021-2023
Sorbonne Université
2014-2023
Inserm
2012-2023
Université Paris Cité
2010-2020
Université de Versailles Saint-Quentin-en-Yvelines
2013-2020
Institut de la Vision
2014-2017
Étude des Structures, des Processus d’Adaptation et des Changements de l’Espace
2014-2016
DEP domain-containing 5 protein (DEPDC5) is a repressor of the recently recognized amino acid-sensing branch mTORC1 pathway. So far, its function in brain remains largely unknown. Germline loss-of-function mutations DEPDC5 have emerged as major cause familial refractory focal epilepsies, with case reports sudden unexpected death epilepsy (SUDEP). Remarkably, fraction patients also develop cortical dysplasia (FCD), neurodevelopmental malformation. We therefore hypothesized that somatic...
Abstract Cortical malformations such as focal cortical dysplasia type II (FCDII) are associated with pediatric drug-resistant epilepsy that necessitates neurosurgery. FCDII results from somatic mosaicism due to post-zygotic mutations in genes of the PI3K-AKT-mTOR pathway, which produce a subset dysmorphic cells clustered within healthy brain tissue. Here we show correlation between epileptiform activity acute slices obtained human surgical tissues and density neurons. We uncovered multiple...
Rationale: Nonsense (premature stop codon) mutations in mRNA for the cystic fibrosis transmembrane conductance regulator (CFTR) cause (CF) approximately 10% of patients. Ataluren (PTC124) is an oral drug that permits ribosomes to readthrough premature codons produce functional protein.Objectives: To evaluate ataluren activity, safety, and pharmacokinetics children with nonsense mutation CF.Methods: Patients were assessed two 28-day cycles, comprising 14 days on off ataluren. took three times...
DEP-domain containing 5 (DEPDC5), encoding a repressor of the mechanistic target rapamycin complex 1 (mTORC1) signaling pathway, has recently emerged as major gene mutated in familial focal epilepsies and cortical dysplasia. Here we established global knockout rat using TALEN technology to investigate vivo impact Depdc5-deficiency. Homozygous Depdc5(-/-) embryos died from embryonic day 14.5 due growth delay. Constitutive mTORC1 hyperactivation was evidenced brains cultured fibroblasts...
Cystic fibrosis transmembrane conductance regulator (CFTR) protein is a chloride channel regulating fluid homeostasis at epithelial surfaces. Its loss of function induces hypohydration, mucus accumulation, and bacterial infections in CF potentially other lung chronic diseases.To test whether neutrophil elastase (NE) neutrophil-mediated inflammation negatively impact CFTR structure function, vitro vivo.Using an adenovirus-CFTR overexpression approach, we showed that NE degrades wild-type...
The diagnosis of cystic fibrosis (CF) is based on a characteristic clinical picture in association with sweat chloride (Cl(-)) concentration greater than 60 mmol/L or the identification two CF-causing mutations. A challenging problem significant number children for whom no definitive possible because they present symptoms suggestive CF, level intermediate range between 30 and mmol/L, only one identified mutation.To investigate function transmembrane conductance regulator (CFTR) protein...
MS-derived oligodendrocytes conserve their ability to fully interact with axons and glial cells in vivo.
<h3>Background</h3> A challenging problem arising from cystic fibrosis (CF) newborn screening is the significant number of infants with hypertrypsinaemia (HIRT) sweat chloride levels in intermediate range and only one or no identified CF-causing mutations. <h3>Objectives</h3> To investigate diagnostic value for CF assessing transmembrane conductance regulator (CFTR) protein function by measuring nasal potential difference children HIRT. <h3>Methods</h3> specially designed protocol was used...
Diffuse bronchiectasis is a common problem in respiratory clinics. We hypothesized that mutations the solute carrier 26A9 (SLC26A9) gene, encoding for chloride (Cl(-)) transporter mainly expressed lungs, may lead to defects mucociliary clearance. describe two missense variants SLC26A9 gene heterozygote patients presenting with diffuse idiopathic : p.Arg575Trp, identified patient also p.Phe508del CFTR gene; and p.Val486Ile. Expression of both mutants Xenopus laevis oocytes abolished...
Induced pluripotent stem cell–derived (iPS-derived) neural precursor cells may represent the ideal autologous cell source for cell-based therapy to promote remyelination and neuroprotection in myelin diseases. So far, therapeutic potential of reprogrammed has been evaluated neonatal demyelinating models. However, repair efficacy safety these not well addressed demyelinated adult CNS, which decreased plasticity scarring. Moreover, it is clear if induced pluripotent–derived have same...
Mitochondrial dysfunction is responsible for hereditary optic neuropathies. We wished to determine whether preserving mitochondrial bioenergetics could prevent neuropathy in a reliable model of glaucoma. DBA/2J mice exhibit elevated intraocular pressure, progressive degeneration their retinal ganglion cells, and that resembles established glaucoma these directly associated with dysfunction: respiratory chain activity was compromised nerves 5 months before neuronal loss began, the amounts...
Mutations in profilin 1 (PFN1) have been identified rare familial cases of Amyotrophic Lateral Sclerosis (ALS). PFN1 is involved multiple pathways that could intervene ALS pathology. However, the specific pathogenic role mutations still not fully understood. We hypothesized play a regulating autophagy and disrupt this function. used patient cells (lymphoblasts) or tissue (post-mortem) carrying (M114T E117G), designed experimental models expressing wild-type mutant (cell lines novel mice...
Neuroglobin (NGB) is considered as an endogenous neuroprotective molecule against stroke, since the protein alleviates adverse effects of hypoxic and ischemic insults. We previously demonstrated functional link between NGB mitochondria it required for respiratory chain function. Thus, here, we evaluated relevance this effect in Harlequin (Hq) mouse strain, which exhibits retinal ganglion cell (RGC) loss optic atrophy due to a complex I (CI) defect. A twofold decrease amounts was observed Hq...
Objective Germline loss‐of‐function mutations in DEPDC5 , and its binding partners ( NPRL2/3 ) of the mammalian target rapamycin (mTOR) repressor GATOR1 complex, cause focal epilepsies increase risk sudden unexpected death epilepsy (SUDEP). Here, we asked whether haploinsufficiency predisposes to primary cardiac defects that could contribute SUDEP therefore impact clinical management patients at high SUDEP. Methods Clinical investigations were performed 16 with pathogenic variants NPRL2 or...
The GGGGCC intronic repeat expansion within C9ORF72 is the most common genetic cause of ALS and FTD. This mutation results in toxic gain function through accumulation expanded RNA foci aggregation abnormally translated dipeptide proteins, as well loss due to impaired transcription . A number vivo vitro models effects have suggested that both mechanisms synergize disease. However, contribution mechanism remains poorly understood. We generated knockdown mice mimic C9-FTD/ALS patients...
The understanding of the excitotoxic processes associated with a severe status epilepticus (SE) is major importance. Changes brain cholesterol homeostasis an emerging candidate for excitotoxicity. We conducted overall analysis both (i) in fluids and tissues from patients SE: blood (n = 63, n 87 controls), CSF 32, 60 post-mortem 8, 8 controls) (ii) mouse model SE induced by intrahippocampal injection kainic acid. 24-hydroxycholesterol levels were decreased acid hippocampus human plasma when...
Abstract Autoimmune encephalitis (AIE) associated with antibodies directed against the leucine-rich glioma inactivated 1 (LGI1) protein is second most common AIE and responsible for deleterious neocortical limbic epileptic seizures. Previous studies demonstrated a pathogenic role of anti-LGI1 via alterations in expression function Kv1 channels AMPA receptors. However, causal link between seizures has never been demonstrated. Here, we attempted to determine human autoantibodies genesis by...
Background Treatments designed to correct cystic fibrosis transmembrane conductance regulator (CFTR) defects must first be evaluated in preclinical experiments the mouse model of (CF). Mice nasal mucosa mimics bioelectric defect seen humans. The use potential difference (VTE) assess ionic transport is a powerful test evaluating restoration CFTR function. Nasal VTE CF mice well characterized for interpretation. Methods We performed measurements large-scale studies two models CF—B6;129 cftr...
Vaginal dryness due to vaginal atrophy is a common complaint of postmenopausal women, interfering with sexual function and quality life. Hormone replacement therapy the only effective but known risks that leave unmet medical needs. A new product, ZP-025 gel, containing purified (dialyzed lyophilized) bovine colostrum, has been developed for treatment secondary atrophy.The study aims investigate effects intravaginal application on using an animal model.Ovariectomized female Sprague-Dawley...
Abstract Background Cystic fibrosis (CF) is caused by mutations in the gene encoding for CF transmembrane conductance regulator (CFTR) protein, which acts as a chloride channel after activation cyclic AMP (cAMP). Newborn screening programs usually consist of an immunoreactive trypsinogen (IRT) assay, followed when IRT elevated testing panel CF-causing mutations. Some children, however, may have persistent hypertrypsinogenemia, only one or no identified CFTR mutation, and sweat concentrations...