A5061938072- Lysosomal Storage Disorders Research
- Cellular transport and secretion
- Neurogenesis and neuroplasticity mechanisms
- RNA regulation and disease
- Trypanosoma species research and implications
- Hearing, Cochlea, Tinnitus, Genetics
- Nerve injury and regeneration
- Proteoglycans and glycosaminoglycans research
- Vestibular and auditory disorders
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Mesenchymal stem cell research
- MicroRNA in disease regulation
- Calcium signaling and nucleotide metabolism
- Biomedical Research and Pathophysiology
- Carbohydrate Chemistry and Synthesis
- Nerve Injury and Rehabilitation
- Parasitic Diseases Research and Treatment
- Glycogen Storage Diseases and Myoclonus
- Nuclear Structure and Function
- Chemokine receptors and signaling
- Polyamine Metabolism and Applications
- Biotin and Related Studies
Institut Pasteur
2012-2024
Inserm
2006-2024
Université Paris Cité
2022-2024
Sorbonne Université
1997-2021
Centre National de la Recherche Scientifique
2003-2019
Pitié-Salpêtrière Hospital
1997
Oligodendrocyte development is controlled by a number of survival and migratory factors. The present study shows that signaling CXCR4 receptor the chemokine CXCL12 regulates migration neural precursors (NP) as well oligodendrocyte progenitors (OP). expressed E14 striatal NP OP generated neurospheres. In CXCR4-defective mice, in neurosphere outgrowth was twofold less than wild-type (WT) mice; radial cell also decreased. contrast, addition to WT increased from sphere dose-dependent manner with...
BackgroundIn mucopolysaccharidosis type IIIB, a lysosomal storage disease causing early onset mental retardation in children, the production of abnormal oligosaccharidic fragments heparan sulfate is associated with severe neuropathology and chronic brain inflammation. We addressed causative links between biochemical, pathological inflammatory disorders mouse model this disease.Methodology/Principal FindingsIn cell culture, oligosaccharides activated microglial cells by signaling through...
ABSTRACT RNA viruses present an extraordinary threat to human health, given their sudden and unpredictable appearance, the potential for rapid spread among population, ability evolve resistance antiviral therapies. The recent emergence of chikungunya virus, Zika Ebola virus highlights struggles contain outbreaks. A significant hurdle is availability antivirals treat infected or protect at-risk populations. While several compounds show promise in vitro vivo , these outbreaks underscore need...
By providing access to affected neurons, human induced pluripotent stem cells (iPSc) offer a unique opportunity model neurodegenerative diseases. We generated iPSc from the skin fibroblasts of children with mucopolysaccharidosis type IIIB. In this fatal lysosomal storage disease, defective α-N-acetylglucosaminidase interrupts degradation heparan sulfate (HS) proteoglycans and induces cell disorders predominating in central nervous system, causing relentless progression toward severe mental...
Hearing loss is a major health concern affecting millions of people worldwide with currently limited treatment options. In clarin-2-deficient Clrn2
Abstract Deafness, the most frequent sensory deficit in humans, is extremely heterogeneous with hundreds of genes involved. Clinical and genetic analyses an extended consanguineous family pre-lingual, moderate-to-profound autosomal recessive sensorineural hearing loss, allowed us to identify CLRN2, encoding a tetraspan protein, as new deafness gene. Homozygosity mapping followed by exome sequencing identified 14.96 Mb locus on chromosome 4p15.32p15.1 containing likely pathogenic missense...
Abstract Neuroinflammation and iron accumulation are hallmarks of a variety adult neurodegenerative diseases. In Sanfilippo syndrome (mucopolysaccharidosis type III, MPSIII, pediatric disease that shares some features with diseases), the progressive heparan sulfate oligosaccharides (HSOs) induces microglia astrocytes to produce pro‐inflammatory cytokines leading severe neuroinflammation. The objectives present study were (1) measure local concentration assess metabolism in brain MPSIIIB...
To study the biology and repair capacities of mouse oligodendroglial cells, we established cultures cells purified from neonatal wild-type 9.6-kb MBP-LacZ transgenic newborn mice cerebral hemispheres as free-floating aggregates in continuous presence neuroblastoma conditioned medium (N1-B104). In vitro analysis indicated that initial cell preparations were enriched oligodendrocyte pre-progenitors expressed PSA-NCAM GAP-43 but not GD3, O4, NF68 or glial fibrillary acidic protein (GFAP)...
Finding ways to enhance remyelination is a major challenge in treating demyelinating diseases. Recent studies have suggested that circulating bone marrow cells can home brain and transdifferentiate into neural cells. To ask whether hematopoietic precursors form myelinating cells, we investigated the neuropoietic potential of embryonic sorted from mouse aorta-gonads-mesonephros (AGM) region. This cell fraction capable long-term reconstitution generates colonies containing multipotential...
Cell pathology in lysosomal storage diseases is characterized by the formation of distended vacuoles with characteristics lysosomes. Our previous studies mucopolysaccharidosis type IIIB (MPSIIIB), a disease which genetic defect induces accumulation undigested heparan sulfate (HS) fragments, led to hypothesis that abnormal lysosome was related events occurring at Golgi level. We reproduced enzyme MPSIIIB HeLa cells using tetracycline-inducible expression shRNAs directed against...
Abstract Behavioral manifestations mark the onset of disease expression in children with mucopolysaccharidosis type III (MPSIII, Sanfilippo syndrome), a genetic disorder resulting from interruption lysosomal degradation heparan sulfate. In mouse model MPSIII B (MPSIIIB), cortical neuron pathology and dysfunction occur several months before neuronal loss are primarily cell autonomous. The gene coding for GAP43, neurite growth potentiator, is overexpressed MPSIIIB cortex, dystrophy was...
Exposure to molds and mycotoxins not only contributes the onset of respiratory disease, it also affects ocular surface. Very few published studies concern evaluation effect mycotoxin exposure on cells. The present study investigates effects aflatoxin B₁ (AFB₁) gliotoxin, two secreted by Aspergillus molds, biological activity human corneal epithelial (HCE) After 24, 48, 72 h exposure, cellular viability inflammatory response were assessed. Both endpoint cell colorimetric assays continuous...
Spinal root avulsion, or section, results in devastating functional sequels. Whereas reconstruction of motor pathways based on neurotization can reduce deficit, associated permanent limb anesthesia limits expected benefit. Sensory pathway after dorsal injury is limited by the inability re-growing central sensory axons to enter spinal cord through an injured root.To provide evidence for reconnection C7 DRG neurons with nervous system (CNS) experimental section adult rats.We assessed a new...
Botulinum neurotoxins (BoNTs) are responsible for severe flaccid paralysis by inhibiting the release of acetylcholine at neuromuscular junctions. BoNT type B (BoNT/B) most often induces mild forms botulism with predominant dysautonomic symptoms. In food borne and intestinal colonisation such as infant botulism, which frequent naturally acquired digestive tract is main entry route BoNTs into organism. We previously showed that BoNT/B translocates through mouse barrier an endocytosis-dependent...
Biochemical disorders in lysosomal storage diseases consist of the interruption metabolic pathways involved recycling degradation products one or several types macromolecules. The progressive accumulation these primary is direct consequence genetic defect and represents initial pathogenic event. Downstream consequences for affected cells include secondary formation histological lesions, which appear as intracellular vacuoles that represent pathological hallmark diseases. Relationships...