A5103262806- Lysosomal Storage Disorders Research
- Cellular transport and secretion
- Carbohydrate Chemistry and Synthesis
- Cancer, Hypoxia, and Metabolism
- Autopsy Techniques and Outcomes
- Global Cancer Incidence and Screening
- Histone Deacetylase Inhibitors Research
- Neurogenetic and Muscular Disorders Research
- Glycogen Storage Diseases and Myoclonus
- Lung Cancer Diagnosis and Treatment
- Climate Change and Health Impacts
- Endoplasmic Reticulum Stress and Disease
- Neonatal Health and Biochemistry
- Cancer Research and Treatments
- Autophagy in Disease and Therapy
- Occupational and environmental lung diseases
- Infant Nutrition and Health
- Trypanosoma species research and implications
- Genetics and Neurodevelopmental Disorders
- Ubiquitin and proteasome pathways
- Biochemical and Molecular Research
- Mosquito-borne diseases and control
- Protein Degradation and Inhibitors
- Biomedical Research and Pathophysiology
- Metabolism, Diabetes, and Cancer
Ospedale Santa Maria della Misericordia di Udine
2017-2025
University of Udine
2013-2024
Fondazione Italiana Fegato
2011
University of Trieste
1999
The MEF2-class IIa histone deacetylase (HDAC) axis operates in several differentiation pathways and numerous adaptive responses. We show here that nuclear active HDAC4 HDAC7 display transforming capability. oncogenic potential depends on the repression of a limited set genes, most which are MEF2 targets. Genes verified as targets MEF2-HDAC also under influence phosphatidylinositol 3-kinase (PI3K)/Akt pathway affects protein stability. A signature target genes identified by this study is...
BackgroundGaucher Disease is caused by mutations of the GBA gene which encodes lysosomal enzyme acid beta-glucosidase (GCase). commonly affect GCase function perturbing its protein homeostasis rather than catalytic activity. Heat shock proteins are well known cytoprotective molecules with functions in and their manipulation has been suggested as a potential therapeutic strategy for GD. The investigational drug arimoclomol, phase II/III clinical trials, well-characterized HSP amplifier...
Niemann-Pick type C (NPC) disease is an autosomal recessive lysosomal storage disorder caused by mutations in NPC1 or NPC2 genes. In 2009, the molecular characterization of 44 NPC Italian patients has been published. Here, we present update genetic findings 105 belonging to 83 unrelated families (77 and 6 NPC2). genes were studied following algorithm recently Eighty-four different five alleles identified. Only two remained non detected. Sixty-two percent due missense variants. The most...
Glucocerebrosidase (GCase) is a lysosomal enzyme that catalyzes the breakdown of glucosylceramide in presence its activator saposin C (SapC). SapC arises from proteolytical cleavage prosaposin (encoded by PSAP gene), which gives rise to four saposins. GCase targeted lysosomes LIMP-2, encoded SCARB2 gene. deficiency causes Gaucher Disease (GD), mainly due biallelic pathogenetic variants GCase-encoding gene, GBA1. However, impairment activity can be rarely caused or LIMP-2 deficiencies. We...
We have previously reported that exposure of SH-SY5Y neuroblastoma cells to unconjugated bilirubin (UCB) resulted in a marked up-regulation the mRNA encoding for Na+ -independent cystine∶glutamate exchanger System Xc− (SLC7A11 and SLC3A2 genes). In this study we demonstrate treated with UCB showed higher cystine uptake due significant specific increase activity Xc−, without contribution others two transporters (XAG− GGT) neurons. The total intracellular glutathione content was 2 folds...
Glycogen storage disease type II (GSDII) is a lysosomal disorder caused by the deficient activity of acid alpha-glucosidase (GAA) enzyme, leading to accumulation glycogen within lysosomes. The has been classified in infantile and late-onset forms. Most patients share splicing mutation c.-32-13T > G intron 1 GAA gene that prevents efficient recognition exon 2 spliceosome. In this study, we have mapped silencers developed antisense morpholino oligonucleotides (AMOs) inhibit those regions...
Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the acid β-glucosidase gene (GBA1). Besides causing GD, GBA1 constitute main genetic risk factor for developing Parkinson’s disease. The molecular basis of neurological manifestations GD remain elusive. However, neuroinflammation has been proposed as a key player this process. We exploited CRISPR/Cas9 technology to edit human monocytic THP-1 cell line develop isogenic model monocytes and...
There are little data on causes of death in extreme aged. We compared, using autopsy findings, main cause death, overall disease status, and accuracy rate clinical diagnoses aged persons dying at younger ages.We reviewed the complete records 114 consecutive inpatients (97 women, 17 men, age range 97-106, mean 99, median 98) who died Trieste, Italy, represented 99% all extreme-aged person deaths hospital 70% area. The control group included 151 patients (66 85 65-74, 70, 70) during same...
Metabolic adaptations are emerging as common traits of cancer cells and tumor progression. In vitro transformation NIH 3T3 allows the analysis metabolic changes triggered by a single oncogene. this work, we have compared induced H-RAS nuclear resident mutant histone deacetylase 4 (HDAC4). RAS-transformed exhibit dominant aerobic glycolytic phenotype characterized up-regulation enzymes, reduced oxygen consumption defect in complex I activity. model transformation, glycolysis is strictly...
Gaucher disease (GD) is an autosomal recessive lysosomal disorder due to beta-glucosidase gene (GBA) mutations. The molecular diagnosis of GD complicated by the presence recombinant alleles originating from a highly homologous pseudogene. Clinical exome sequencing (CES) rapid genetic approach for identifying disease-causing However, copy number variation and recombination events are poorly detected, further investigations required avoid mis-genotyping. aim this work was set-up integrated...
Pompe disease (PD) is an autosomal recessive lysosomal storage disorder due to deficient activity of the acid alpha glucosidase enzyme (GAA). As a consequence enzymatic defect, undigested glycogen accumulates within lysosomes. Most patients affected by late-onset (LO) phenotype carry in at least one allele c.-32-13T>G variant, which leads exon 2 exclusion from pre-mRNA. These display variable and suboptimal response replacement therapy. To identify novel therapeutic approaches, we developed...
Abstract Gaucher Disease (GD) is caused by mutations of the GBA gene which encodes lysosomal enzyme acid beta-glucosidase (GCase). commonly affect GCase function perturbing its protein homeostasis rather than catalytic activity. Heat shock proteins (HSPs) are well known cytoprotective molecules with numerous functions in and their manipulation has been suggested as a potential therapeutic strategy for GD. The investigational drug arimoclomol, currently phase II/III clinical trials,...