6 results on '"Egesipe, A-L"'
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2. Micropatterned substrates to accelerate pathological smooth muscle cells aging
- Author
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Pereira, P., Estronca, L., Vazão, H., Egesipe, A. -L., Nissan, X., Ferreira, L., and Universidade do Minho
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Ciências Médicas::Biotecnologia Médica - Abstract
FEDER through the Program COMPETE (Centro-07-ST24-FEDER-002008) and of FCT (SFRH/BD/71042/2010; EXPL/BIM-MED/2267/2013) and to UID/NEU/04539/2013), info:eu-repo/semantics/publishedVersion
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- 2016
3. Drug screening on Hutchinson Gilford progeria pluripotent stem cells reveals aminopyrimidines as new modulators of farnesylation
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Blondel, S, primary, Egesipe, A-L, additional, Picardi, P, additional, Jaskowiak, A-L, additional, Notarnicola, M, additional, Ragot, J, additional, Tournois, J, additional, Le Corf, A, additional, Brinon, B, additional, Poydenot, P, additional, Georges, P, additional, Navarro, C, additional, pitrez, P R, additional, Ferreira, L, additional, Bollot, G, additional, Bauvais, C, additional, Laustriat, D, additional, Mejat, A, additional, De Sandre-Giovannoli, A, additional, Levy, N, additional, Bifulco, M, additional, Peschanski, M, additional, and Nissan, X, additional
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- 2016
- Full Text
- View/download PDF
4. Metformin decreases progerin expression and alleviates pathological defects of Hutchinson–Gilford progeria syndrome cells
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Marc Peschanski, Anne-Laure Jaskowiak, Nicolas Lévy, Anne-Laure Egesipe, Sophie Blondel, Xavier Nissan, Alessandra Lo Cicero, Annachiara De Sandre-Giovannoli, Claire Navarro, Egesipe A.-L., Blondel S., Lo Cicero A., Jaskowiak A.-L., Navarro C., De Sandre-Giovannoli A., Levy N., Peschanski M., and Nissan X.
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0301 basic medicine ,Premature aging ,congenital, hereditary, and neonatal diseases and abnormalities ,Aging ,Article ,LMNA ,03 medical and health sciences ,Progeria ,0302 clinical medicine ,medicine ,Induced pluripotent stem cell ,integumentary system ,business.industry ,Genetic disorder ,nutritional and metabolic diseases ,medicine.disease ,Progerin ,Metformin ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,Geriatrics and Gerontology ,business ,Lamin ,medicine.drug - Abstract
Hutchinson–Gilford progeria syndrome (HGPS) is a rare genetic disorder that causes systemic accelerated aging in children. This syndrome is due to a mutation in the LMNA gene that leads to the production of a truncated and toxic form of lamin A called progerin. Because the balance between the A-type lamins is controlled by the RNA-binding protein SRSF1, we have hypothesized that its inhibition may have therapeutic effects for HGPS. For this purpose, we evaluated the antidiabetic drug metformin and demonstrated that 48 h treatment with 5 mmol/l metformin decreases SRSF1 and progerin expression in mesenchymal stem cells derived from HGPS induced pluripotent stem cells (HGPS MSCs). The effect of metformin on progerin was then confirmed in several in vitro models of HGPS, i.e., human primary HGPS fibroblasts, LmnaG609G/G609G mouse fibroblasts and healthy MSCs previously treated with a PMO (phosphorodiamidate morpholino oligonucleotide) that induces progerin. This was accompanied by an improvement in two in vitro phenotypes associated with the disease: nuclear shape abnormalities and premature osteoblastic differentiation of HGPS MSCs. Overall, these results suggest a novel approach towards therapeutics for HGPS that can be added to the currently assayed treatments that target other molecular defects associated with the disease. A diabetes drug with a proven track record in the clinic may also offer an alternative treatment for a rare 'premature aging' disorder. A genetic mutation in patients with Hutchinson-Gilford progeria syndrome (HGPS) produces a defective protein called progerin, which causes children to develop skeletal, cardiovascular and other symptoms normally seen in the elderly. Researchers led by Xavier Nissan at I-Stem in France have demonstrated that metformin triggers a biochemical 'switch' that causes cells to decrease their production of progerin, and instead generate an alternative, non-toxic protein. Relative to untreated cells, metformin-treated cells were less prone to develop structural abnormalities or undergo premature maturation. Importantly, doctors have used metformin for over 20 years, suggesting that such a treatment approach should be safe for HGPS patients.
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- 2016
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- View/download PDF
5. A High Throughput Phenotypic Screening reveals compounds that counteract premature osteogenic differentiation of HGPS iPS-derived mesenchymal stem cells
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Xavier Nissan, Anne-Laure Jaskowiak, Alessandra Lo Cicero, Anne-Laure Egesipe, Benjamin Brinon, Annachiara De Sandre-Giovannoli, Lino Ferreira, Nicolas Lévy, Johana Tournois, Patrícia R. Pitrez, CECS/I-Stem, Association française contre les myopathies (AFM-Téléthon), Institut des cellules souches pour le traitement et l'étude des maladies monogéniques (I-STEM), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, Therapie Cellulaire en Pathologie Cardio-Vasculaire (UMR_S 633), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Etude des Cellules Souches (CECS), Association française contre les myopathies ( AFM-Téléthon ), Institut des cellules souches pour le traitement et l'étude des maladies monogéniques ( I-STEM ), Université d'Évry-Val-d'Essonne ( UEVE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Therapie Cellulaire en Pathologie Cardio-Vasculaire ( UMR_S 633 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Génétique Médicale et Génomique Fonctionnelle ( GMGF ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre d'Etude des Cellules Souches ( CECS ), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Lo Cicero A., Jaskowiak A.-L., Egesipe A.-L., Tournois J., Brinon B., Pitrez P.R., Ferreira L., De Sandre-Giovannoli A., Levy N., and Nissan X.
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0301 basic medicine ,Cell type ,congenital, hereditary, and neonatal diseases and abnormalities ,Phenotypic screening ,Induced Pluripotent Stem Cells ,Retinoic acid ,Tretinoin ,Biology ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Progeria ,Osteogenesis ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,medicine ,Humans ,Induced pluripotent stem cell ,Child ,Isotretinoin ,Genetics ,Multidisciplinary ,integumentary system ,Guided Tissue Regeneration ,Mesenchymal stem cell ,nutritional and metabolic diseases ,Aging, Premature ,Cell Differentiation ,Mesenchymal Stem Cells ,medicine.disease ,Progerin ,Alkaline Phosphatase ,Lamin Type A ,3. Good health ,Cell biology ,High-Throughput Screening Assays ,030104 developmental biology ,chemistry ,Gene Expression Regulation ,[ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Alkaline phosphatase - Abstract
Hutchinson-Gilford progeria syndrome (HGPS) is a rare fatal genetic disorder that causes systemic accelerated aging in children. Thanks to the pluripotency and self-renewal properties of induced pluripotent stem cells (iPSC), HGPS iPSC-based modeling opens up the possibility of access to different relevant cell types for pharmacological approaches. In this study, 2800 small molecules were explored using high-throughput screening, looking for compounds that could potentially reduce the alkaline phosphatase activity of HGPS mesenchymal stem cells (MSCs) committed into osteogenic differentiation. Results revealed seven compounds that normalized the osteogenic differentiation process and, among these, all-trans retinoic acid and 13-cis-retinoic acid, that also decreased progerin expression. This study highlights the potential of high-throughput drug screening using HGPS iPS-derived cells, in order to find therapeutic compounds for HGPS and, potentially, for other aging-related disorders.
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- 2016
- Full Text
- View/download PDF
6. Drug screening on Hutchinson Gilford progeria pluripotent stem cells reveals aminopyrimidines as new modulators of farnesylation
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Patrícia R. Pitrez, Anne-Laure Jaskowiak, G. Bollot, Benjamin Brinon, C. Bauvais, Paola Picardi, A. Mejat, Johana Tournois, Maurizio Bifulco, Anne-Laure Egesipe, Lino Ferreira, A. Le Corf, J. Ragot, Marc Peschanski, Sophie Blondel, A. De Sandre-Giovannoli, P. Poydenot, P. Georges, D. Laustriat, Claire Navarro, Xavier Nissan, M. Notarnicola, Nicolas Lévy, Institut des cellules souches pour le traitement et l'étude des maladies monogéniques (I-STEM), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, Università degli Studi di Salerno = University of Salerno (UNISA), IRCCS 'De Bellis', Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Universidade de Coimbra [Coimbra], Synsight, Laboratoire de biologie et modélisation de la cellule (LBMC UMR 5239), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), FCOMP-01-2014-FEDER-041659, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Gall, Valérie, Università degli Studi di Salerno (UNISA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), Blondel, S, Egesipe, A-L, Picardi, P, Jaskowiak, A-L, Notarnicola, M, Ragot, J, Tournois, J, Le Corf, A, Brinon, B, Poydenot, P, Georges, P, Navarro, C, Pitrez, P R, Ferreira, L, Bollot, G, Bauvais, C, Laustriat, D, Mejat, A, De Sandre-Giovannoli, A, Levy, N, Bifulco, Maurizio, Peschanski, M, and Nissan, X
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0301 basic medicine ,Cancer Research ,Farnesyl pyrophosphate ,LMNA ,chemistry.chemical_compound ,0302 clinical medicine ,Progeria ,Osteogenesis ,Stem cell ,integumentary system ,Cell Differentiation ,Geranyltranstransferase ,Lamin Type A ,Progerin ,farnesylation ,3. Good health ,Molecular Docking Simulation ,Biochemistry ,030220 oncology & carcinogenesis ,[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Protein farnesylation ,Original Article ,lipids (amino acids, peptides, and proteins) ,Pluripotent Stem Cells ,Premature aging ,congenital, hereditary, and neonatal diseases and abnormalities ,Immunology ,Protein Prenylation ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Biology ,[SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics ,Small Molecule Libraries ,Structure-Activity Relationship ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,medicine ,Farnesyltranstransferase ,Humans ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,Binding Sites ,organic chemicals ,nutritional and metabolic diseases ,Cell Biology ,medicine.disease ,Protein Structure, Tertiary ,Farnesylation Process ,Pyrimidines ,030104 developmental biology ,chemistry ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,aminopyrimidines ,Cancer research ,[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology ,Protein prenylation - Abstract
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by a dramatic appearance of premature aging. HGPS is due to a single-base substitution in exon 11 of the LMNA gene (c.1824C>T) leading to the production of a toxic form of the prelamin A protein called progerin. Because farnesylation process had been shown to control progerin toxicity, in this study we have developed a screening method permitting to identify new pharmacological inhibitors of farnesylation. For this, we have used the unique potential of pluripotent stem cells to have access to an unlimited and relevant biological resource and test 21 608 small molecules. This study identified several compounds, called monoaminopyrimidines, which target two key enzymes of the farnesylation process, farnesyl pyrophosphate synthase and farnesyl transferase, and rescue in vitro phenotypes associated with HGPS. Our results opens up new therapeutic possibilities for the treatment of HGPS by identifying a new family of protein farnesylation inhibitors, and which may also be applicable to cancers and diseases associated with mutations that involve farnesylated proteins.
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- 2016
- Full Text
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