A5042710643- Genetics and Neurodevelopmental Disorders
- Hepatitis C virus research
- Monoclonal and Polyclonal Antibodies Research
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Autism Spectrum Disorder Research
- Hepatitis B Virus Studies
- HIV/AIDS drug development and treatment
- Protein Kinase Regulation and GTPase Signaling
- CRISPR and Genetic Engineering
- Cholinesterase and Neurodegenerative Diseases
- Bipolar Disorder and Treatment
- Lipid metabolism and biosynthesis
- RNA Research and Splicing
- Metabolism and Genetic Disorders
- Endoplasmic Reticulum Stress and Disease
- Epigenetics and DNA Methylation
- Peroxisome Proliferator-Activated Receptors
- HIV Research and Treatment
- Fatty Acid Research and Health
- Congenital heart defects research
- Pancreatic function and diabetes
- Neuroscience and Neuropharmacology Research
- Biochemical and Molecular Research
- RNA regulation and disease
University of Rome Tor Vergata
2015-2024
Saint Camillus International University of Health and Medical Sciences
2021-2024
IRBM Science Park
2003-2009
Merck & Co., Inc., Rahway, NJ, USA (United States)
2009
Università Cattolica del Sacro Cuore
2006
Istituto di Genetica Molecolare
1997
University of Pisa
1993
ABSTRACT The RNA-dependent RNA polymerase of hepatitis C virus (HCV) is the catalytic subunit viral amplification machinery and an appealing target for development new therapeutic agents against HCV infection. Nonnucleoside inhibitors based on a benzimidazole scaffold have been recently reported. Compounds this class are efficient replication in cell culture, thus providing attractive candidates further development. Here we report detailed analysis mechanism action selected inhibitors....
Activity-dependent protein synthesis at synapses is dysregulated in the Fragile X syndrome (FXS). This process contributes to dendritic spine dysmorphogenesis and synaptic dysfunction FXS. Matrix Metalloproteinase 9 (MMP-9) an enzyme involved activity-dependent reorganization of architecture was shown regulate morphology a mouse model FXS, Fmr1 knock-out mice. Here we show that MMP-9 mRNA part FMRP complex colocalizes dendrites. In absence translation increased synapses, suggesting this...
Abstract The molecular signature underlying autism spectrum disorder remains largely unknown. This study identifies differential expression of mTOR and MAPK pathways in patients affected by mild severe idiopathic autism. A total 55 subjects were enrolled, which 22 typically developing individuals 33 aged between 3 11 years, with disorder. detailed history, including physical examination, developmental evaluation, mental health history diagnostic observation schedule performed for each...
The NS2 protein of hepatitis C virus (HCV) is released from its polyprotein precursor by two proteolytic cleavages. N terminus this separated the E2/p7 polypeptide a cleavage thought to be mediated signal peptidase, whereas NS2-3 junction located at processed viral protease. To characterize biogenesis encoded BK strain HCV, we have defined minimal region required for efficient site and analyzed interaction mature with membrane endoplasmic reticulum (ER). We observed that although can occur...
Fragile X syndrome (FXS) is a monogenic form of intellectual disability and autism spectrum disorder caused by the absence fragile mental retardation protein (FMRP). In biological models for disease, this leads to upregulated mRNA translation as consequence, deficits in synaptic architecture plasticity. Preclinical studies revealed that pharmacological interventions restore those deficits, which are thought mediate FXS cognitive behavioral symptoms. Here, we characterized de novo rate...
ABSTRACT The hepatitis C virus (HCV) serine protease is necessary for viral replication and represents a valid target developing new therapies HCV infection. Potent selective inhibitors of this enzyme have been identified shown to inhibit in tissue culture. optimization these clinical development would greatly benefit from vitro systems the identification study resistant variants. We report use subgenomic replicons isolate characterize mutants inhibitor. Taking advantage replicons' ability...
Processing at the C terminus of NS2 protein hepatitis virus (HCV) is mediated by a virus-encoded protease which spans most and part NS3 polypeptide. In vitro cotranslational cleavage 2-3 junction stimulated presence microsomal membranes ultimately results in membrane insertion To characterize biochemical properties this viral protease, we have established an assay whereby NS2-3 HCV BK can be activated posttranslationally addition detergents. The proficiency several deletion single point...
The fragile X syndrome (FXS), the most common form of inherited intellectual disability, is due to absence FMRP, a protein regulating RNA metabolism. Recently, an unexpected function FMRP in modulating activity Adenosine Deaminase Acting on (ADAR) enzymes has been reported both Drosophila and Zebrafish. ADARs are RNA-binding proteins that increase transcriptional complexity through post-transcriptional mechanism called editing. To evaluate ADAR2-FMRP interaction mammals we analyzed several...
Abstract The fragile X mental retardation protein (FMRP) is lacking or mutated in patients with the syndrome (FXS), most frequent form of inherited intellectual disability. FMRP affects metastasis formation a mouse model for breast cancer. Here we show that overexpressed human melanoma high Breslow thickness and Clark level. Furthermore, meta-analysis TCGA data revealed levels expression correlate significantly metastatic tumor tissues, risk relapsing disease-free survival. Reduction cell...
Converging evidence indicates that the Fragile X Messenger Ribonucleoprotein (FMRP), which absent or mutated in Syndrome (FXS), plays a role many types of cancers. However, while FMRP roles brain development and function have been extensively studied, its involvement biology tumors remains largely unexplored. Here we show, human glioblastoma (GBM) biopsies, increased expression directly correlates with worse patient outcome. In contrast, reductions correlate diminished tumor growth...
Article24 July 2020Open Access Source DataTransparent process Spatial control of nucleoporin condensation by fragile X-related proteins Arantxa Agote-Aran Institut de Génétique et Biologie Moléculaire Cellulaire (IGBMC), Illkirch, France Centre National la Recherche Scientifique UMR 7104, Strasbourg, Santé Médicale U964, Université Search for more papers this author Stephane Schmucker Katerina Jerabkova Inès Jmel Boyer Alessandro Berto Jacques Monod, CNRS UMR7592-Université Paris Diderot,...
Abstract In fragile X syndrome (FXS) the lack of mental retardation protein (FMRP) leads to exacerbated signaling through metabotropic glutamate receptors 5 (mGlu5Rs). The adenosine A 2A (A Rs), modulators neuronal damage, could play a role in FXS. synaptic colocalization and strong permissive interaction between mGlu5 hippocampus have been previously reported, suggesting that blocking Rs might normalize mGlu5R-mediated effects To study cross-talk absence FMRP, we performed extracellular...
Friedreich's ataxia is an autosomal-recessive cerebellar caused by mutation of the frataxin gene, resulting in decreased expression, mitochondrial dysfunction, and oxidative stress. Currently, no treatment available for patients. Given that levels residual critically affect disease severity, main goal a specific therapy to increase levels.With aim accelerate development new ataxia, we took drug repositioning approach identify market-available drugs able levels.Using cell-based reporter assay...
Naturally occurring hepatitis C virus (HCV) subgenomic RNAs have been found in several HCV patients. These deletion mutants, mostly lacking the genes encoding envelope glycoproteins, were both liver and serum, where their relatively high abundance suggests that they are capable of autonomous replication can be packaged secreted viral particles, presumably harboring proteins from wild type coinfecting same cell. We recapitulated some these natural deletions context isolate JFH-1 confirmed...
Fragile X syndrome (FXS) is the most common form of monogenic intellectual disability and autism, caused by absence functional fragile messenger ribonucleoprotein 1 (FMRP). FXS features include increased dysregulated protein synthesis, observed in both murine human cells. Altered processing amyloid precursor (APP), consisting an excess soluble APPα (sAPPα), may contribute to this molecular phenotype mice fibroblasts. Here we show age-dependent dysregulation APP fibroblasts from individuals,...
The finely tuned regulation of mitochondria activity is essential for proper brain development. Fragile X Syndrome (FXS), the leading cause inherited intellectual disability, a neurodevelopmental disorder in which mitochondrial dysfunction has been increasingly implicated. This study investigates role Glycogen Synthase Kinase 3β (GSK3β) FXS. Several studies have reported dysregulation GSK3β FXS, and its function also well established. However, link between disrupted FXS remains unexplored....
Abstract: The incorporation and redistribution of [1‐ 14 C]arachidonic acid in SK‐N‐BE human neuroblastoma cell phospholipids were investigated. By continuous labelling serum‐enriched medium, a rapid radioactivity into phosphatidylcholine (PtdCho), phosphatidylinositol, phosphatidylserine was observed; initially, phosphatidylethanolamine (PtdEtn) poorly labelled, but at later stages it displayed the highest level arachidonic incorporation, comparison with other phospholipid classes....
The effects of the local anaesthetics procaine, tetracaine and lidocaine antidepressant imipramine on human erythrocyte acetylcholinesterase were investigated. All four amphiphilic drugs inhibited enzymic activity, IC50 (the concentration causing 50% inhibition) being about 0.40 mM for 0.05 tetracaine, 0.70 7.0 lidocaine. Procaine activity competitively at concentrations which they did not perturb physical state membrane lipid environment, as assessed by steady-state fluorescence...
Breast cancer is the most common among women worldwide. Molecular and clinical evidence indicated that Fragile X Messenger Ribonucleoprotein 1 (FMRP) plays a role in different types of cancer, including breast cancer. FMRP an RNA binding protein regulates metabolism large group mRNAs coding for proteins involved both neural processes epithelial-mesenchymal transition, pivotal mechanism associated to tumor progression, aggressiveness chemoresistance. Here, we carried out retrospective...
The hepatitis C virus (HCV) NS3 protease cleaves the viral polyprotein at specific sites to release putative components of HCV replication machinery. Selective inhibition this enzyme is predicted block replication, and thus considered an attractive candidate for development anti-HCV therapeutics. To set up a system analysis activity in cultured cells, we constructed family chimeric Sindbis viruses which carry sequences coding its activator, NS4A, their genomes. were fused gene structural via...