A5043190376- Neurogenesis and neuroplasticity mechanisms
- Nerve injury and regeneration
- Neuroinflammation and Neurodegeneration Mechanisms
- Multiple Sclerosis Research Studies
- Chemokine receptors and signaling
- Bioinformatics and Genomic Networks
- Gene Regulatory Network Analysis
- Computational Drug Discovery Methods
- interferon and immune responses
- Immune cells in cancer
- Hereditary Neurological Disorders
- Axon Guidance and Neuronal Signaling
- T-cell and B-cell Immunology
- Mesenchymal stem cell research
- Immune responses and vaccinations
- Immune Response and Inflammation
- Sphingolipid Metabolism and Signaling
- Biomedical Text Mining and Ontologies
- Immunotherapy and Immune Responses
- Blind Source Separation Techniques
- Peroxisome Proliferator-Activated Receptors
- Inflammasome and immune disorders
- Tensor decomposition and applications
- NF-κB Signaling Pathways
- Nuclear Receptors and Signaling
Institut du Cerveau
2012-2025
Sorbonne Université
2014-2025
Centre National de la Recherche Scientifique
2014-2025
Assistance Publique – Hôpitaux de Paris
2007-2025
Inserm
2014-2025
CentraleSupélec
2024
Université Paris-Saclay
2024
Allen Institute for Brain Science
2018-2019
Canadian Nautical Research Society
2019
Université Paris Cité
2014-2017
Among the chemokine family, fractalkine shows unusual properties: it exists as a membrane-bound and soluble protein, both its receptor CX(3)CR1 are expressed predominantly in central nervous system. In rat cell culture models, was neurons microglia, but not astrocytes exclusively localized to microglial cells, where expression downregulated by treatment with bacterial endotoxin (LPS). cultures, LPS (10 ng/ml) induced marked increase release of proinflammatory cytokine tumor necrosis...
One major challenge in multiple sclerosis is to understand the cellular and molecular mechanisms leading disease severity progression. The recently demonstrated correlation between remyelination emphasizes importance of identifying factors a favourable outcome. Why fails or succeeds patients remains largely unknown, mainly because has never been studied within humanized pathological context that would recapitulate events plaque formation such as infiltration inflammatory cells. Therefore, we...
Myelin regeneration (remyelination) in the CNS depends on recruitment, proliferation and differentiation of oligodendrocyte precursor cells (OPCs) at demyelinated lesions. However, despite presence OPCs, very few oligodendrocytes myelin are regenerated chronic multiple sclerosis (MS) lesions for reasons that remain poorly understood. Here, using a spontaneous remyelination model mice, we found retinaldehyde dehydrogenase 2 (Raldh2), rate-limiting enzyme retinoic acid (RA) synthesis, is...
Boundary cap cells (BC), which express the transcription factor Krox20, participate in formation of boundary between central nervous system and peripheral system. To study BC stemness, we developed a method to purify amplify vitro from Krox20 Cre/+ , R26R YFP/+ mouse embryos. We show that progeny are EGF/FGF2-responsive, form spheres, neural crest markers. Upon growth withdrawal, gave rise multiple CNS lineages. Transplanted into developing murine forebrain, they successfully survived,...
Abstract During development, boundary cap cells (BC) and neural crest cell (NCC) derivatives generate Schwann (SC) of the spinal roots a subpopulation neurons satellite in dorsal root ganglia. Despite their stem-like properties, therapeutic potential diseased central nervous system (CNS) was never explored. The aim this work to explore BC for CNS remyelination. We derived from Krox20Cre × R26RYfp embryos at E12.5, when Krox20 is exclusively expressed by BC. Combining microdissection fate...
Pelizaeus-Merzbacher disease (PMD) results from an X-linked misexpression of proteolipid protein 1 (PLP1). This leukodystrophy causes severe hypomyelination with progressive inflammation, leading to neurological dysfunctions and shortened life expectancy. While no cure exists for PMD, experimental cell-based therapy in the dysmyelinated shiverer model suggested that human oligodendrocyte progenitor cells (hOPCs) or neural precursor (hNPCs) are promising candidates treat myelinopathies....
Much evidence suggests that apoptosis plays a crucial role in cell population homeostasis depends on the expression of various genes implicated control life and death. The sensitivity human neuroblastoma cells SK‐N‐SH to undergo induced by thapsigargin was examined. were previously differentiated into neuronal treatments with retinoic acid (RA), 4β‐phorbol 12‐myristate 13‐acetate (PMA) which increases protein kinase C (PKC) activity, staurosporine decreases PKC activity. Neuronal...
Recent findings suggested that inducing neural cell adhesion molecule polysialylation in rodents is a promising strategy for promoting tissue repair the injured central nervous system. Since autologous grafting of Schwann cells one potential to promote system remyelination, it essential show such can be translated adult primate and interest myelin diseases. Adult macaque were transduced with lentiviral vector encoding sialyltransferase, an enzyme responsible polysialylation. In vitro, we...
Remyelination of CNS axons by Schwann cells (SCs) is not efficient, in part due to the poor migration SCs into adult CNS. Although it known that migrating avoid white matter tracts, molecular mechanisms underlying this exclusion have never been elucidated. We now demonstrate myelin-associated glycoprotein (MAG), a well inhibitor neurite outgrowth, inhibits rat SC and induces their death via γ-secretase-dependent regulated intramembrane proteolysis p75 neurotrophin receptor (also as...
Schwann cells (SC) enter the central nervous system (CNS) in pathophysiological conditions. However, how SC invade CNS to remyelinate axons remains undetermined. We studied migratory behavior ex vivo and after exogenous transplantation demyelinated spinal cord. The data highlight for first time that migrate preferentially along blood vessels perivascular extracellular matrix (ECM), avoiding myelin. demonstrate vitro this migration route occurs by virtue of a dual mode action Eph/ephrin...
Abstract Facial nerve axotomy (FNA) is a well‐established experimental model of motoneuron regeneration. After peripheral axotomy, sequence events including glial activation and axonal regrowth leads to functional recovery the afflicted pool motoneurons. Using microarray analysis we identified an increase in expression 60 genes (at false discovery rate 0.1, were significant P < 0.004) within facial nucleus as consequence injury. In situ hybridization validated increased many these...
Abstract It has been proposed that the adult dorsal root ganglia (DRG) harbor neural stem/progenitor cells (NPCs) derived from crest. However, thorough characterization of their stemness and differentiation plasticity was not addressed. In this study, we investigated DRG-NPC stem cell properties overtime, fate when ectopically grafted in central nervous system. We compared them vitro vivo to well-characterized spinal cord-NPCs same donors. Using micro-dissection neurosphere cultures,...
Schwann cell (SC) transplantation is currently being discussed as a strategy that may promote functional recovery in patients with multiple sclerosis (MS) and other inflammatory demyelinating diseases of the central nervous system (CNS). However this assumes they will not only survive but also remyelinate demyelinated axons chronically inflamed CNS. To address question we investigated fate transplanted SCs myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune...
Elevated levels of saturated very long-chain fatty acids (VLCFAs) in cell membranes and secreted lipoparticles have been associated with neurotoxicity and, therefore, require tight regulation. Excessive VLCFAs are imported into peroxisomes for degradation by β-oxidation. Impaired VLCFA catabolism due to primary or secondary peroxisomal alterations is featured neurodegenerative neuroinflammatory disorders such as X-linked adrenoleukodystrophy multiple sclerosis (MS). Here, we identified that...
Fractalkine (FKN/CX3CL1) is a cell surface-expressed chemokine involved in many aspects of leukocyte trafficking and activation. The various structural domains FKN play distinct roles its ability to bind activate receptor, CX3CR1. A human herpesvirus 8-encoded chemokine, termed viral macrophage inflammatory protein (vMIP)-II, structurally similar FKN; vMIP-II nonselective receptor antagonist (binding multiple receptors, including CX3CR1). goal this study was identify determinants selectivity...
Abstract The polygenic and multi-cellular nature of multiple sclerosis (MS) immunopathology necessitates cell-type-specific molecular studies in order to improve our understanding the diverse mechanisms underlying immune cell dysfunction MS. Here, by generating a dataset 1,075 transcriptomes from 209 participants (167 MS 42 healthy), we assessed MS-associated transcriptional changes six implicated cell-type-states: naïve memory helper T cells classical monocytes purified peripheral blood,...
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We introduce a novel tree-based method for visualizing molecular conformation sampling. Our offers enhanced precision in highlighting conformational differences and facilitates the observation of local minimas within proteins fold space. The projection empirical laboratory data on tree allows us to create link between protein conformations disease relevant data. To demonstrate efficacy our approach, we applied it ATP-binding cassette subfamily D member 1 (ABCD1) transporter responsible very...
In multiple sclerosis (MS), immune cells invade the CNS and destroy myelin. Macrophages contribute to demyelination myelin repair, their role in each process depends on ability acquire specific phenotypes response external signals. this article, we assess whether defects MS patient macrophage responses may lead increased inflammation or lack of neuroregenerative effects.