A5031439743- Lysosomal Storage Disorders Research
- Cellular transport and secretion
- Trypanosoma species research and implications
- Calcium signaling and nucleotide metabolism
- Carbohydrate Chemistry and Synthesis
- CRISPR and Genetic Engineering
- Studies on Chitinases and Chitosanases
- Cardiomyopathy and Myosin Studies
- Biotechnology and Related Fields
- Parkinson's Disease Mechanisms and Treatments
- Business and Management Studies
- Sphingolipid Metabolism and Signaling
- Glycogen Storage Diseases and Myoclonus
- Child Nutrition and Feeding Issues
- Education and Public Policy
- Advanced biosensing and bioanalysis techniques
- Geography and Environmental Studies
- Fish biology, ecology, and behavior
- Infant Nutrition and Health
- Blood disorders and treatments
- Occupational Health and Safety Research
- Biochemical and Molecular Research
- Occupational Health and Performance
- Neurological diseases and metabolism
- Corneal Surgery and Treatments
National Institute of Health Dr. Ricardo Jorge
2017-2025
Universidade do Porto
2004-2020
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto
2015-2020
Instituto Nacional de Saúde
2020
Leiden University
2017-2018
Universidade Lusófona
2013-2017
Academic Medical Center
2013-2016
Instituto de Biologia Molecular e Celular
2014
Institut de Biologie Moléculaire et Cellulaire
2011
Centro de Genética Clínica
2005
Significance Our report highlights, for the first time to our knowledge, a distinct relationship between lysosomal integral membrane protein type-2 (LIMP-2) expression, β-glucocerebrosidase (GC) activity, and clearance of α-synuclein. In LIMP-2–deficient mice, increased levels endogenous α-synuclein led severe neurological deficits premature death. We found that loss LIMP-2 reduced GC resulting in lipid storage, disturbed autophagic/lysosomal function, accumulation leading neurotoxicity...
The main clinical features of two siblings from a consanguineous marriage were progressive myoclonic epilepsy without intellectual impairment and nephrotic syndrome with strong accumulation C1q in capillary loops mesangium kidney. biochemical analysis one the patients revealed normal β-glucocerebrosidase activity leukocytes, but severe enzymatic deficiency cultured skin fibroblasts. This suggested defect intracellular sorting pathway this enzyme. sequence gene encoding LIMP-2 (SCARB2),...
The membrane lipid glucosylceramide (GlcCer) is continuously formed and degraded. Cells express two GlcCer-degrading β-glucosidases, glucocerebrosidase (GBA) GBA2, located in outside the lysosome, respectively. Here we demonstrate that through transglucosylation both GBA GBA2 are able to catalyze vitro transfer of glucosyl-moieties from GlcCer cholesterol, vice versa. Furthermore, natural occurrence 1-O-cholesteryl-β-D-glucopyranoside (GlcChol) mouse tissues human plasma demonstrated using...
Gaucher disease is caused by inherited deficiency of lysosomal glucocerebrosidase. Proteome analysis laser-dissected splenic cells revealed increased amounts glycoprotein nonmetastatic melanoma protein B (gpNMB). Plasma gpNMB was also elevated, correlating with chitotriosidase and CCL18, which are established markers for human cells. In mice, produced Correction glucocerebrosidase in mice gene transfer or pharmacological substrate reduction reverses abnormalities. conclusion, acts as a...
Mucopolysaccharidosis type IIIC is a neurodegenerative lysosomal storage disorder (LSD) characterized by the accumulation of undegraded heparan sulfate (HS) due to lack an enzyme responsible for its degradation: acetyl-CoA:α-glucosaminide N-acetyltransferase (HGSNAT). Classical treatments are ineffective. Here, we attempt new approach in genetic medicine, substrate reduction therapy (gSRT), counteract this neurological disorder. Briefly, used synthetic oligonucleotides, particularly gapmer...
Abstract Background Fabry disease (FD), an X-linked lysosomal storage disorder, is caused by a reduced activity of the enzyme α-galactosidase A. The disorder ultimately leads to organ damage (including renal failure) in males and females. However, heterozygous females usually present milder phenotype with later onset slower progression. Methods A combined enzymatic genetic strategy was used, measuring genotyping gene ( GLA ) dried blood samples (DBS) 911 patients undergoing haemodialysis...
Knowledge on clinical profiles of late-onset phenotypes Fabry disease (FD) is essential to better define their natural history. Our study aims demonstrate a founder effect FD due the GLA gene mutation c.337T>C (p.F113L) in Portuguese region Guimarães; and characterize profile this phenotype large cohort genetically related adult patients, living same region.FD screening was performed 150 patients with hypertrophic cardiomyopathy (HCM) found 25 (16.6%). The p.F113L 21 them, leading genealogy...
We studied 21 patients, from 18 families, with L-2-hydroxyglutaric aciduria (L-2-HGA), a rare neurometabolic disorder homogeneous presentation: progressive neurodegeneration extrapyramidal and cerebellar signs, seizures, subcortical leukoencephalopathy. Increased levels of acid in body fluids proved the diagnosis L-2-HGA all patients. analyzed gene (L2HGDH), recently found to be mutated consanguineous families L-2-HGA, identified seven novel mutations 15 families. Three appeared particularly...
Lysosomal integral membrane protein-2 (LIMP2) mediates trafficking of glucocerebrosidase (GBA) to lysosomes. Deficiency LIMP2 causes action myoclonus-renal failure syndrome (AMRF). LIMP2-deficient fibroblasts virtually lack GBA like the cells patients with Gaucher disease (GD), a lysosomal storage disorder caused by mutations in gene. While GD is characterized presence glucosylceramide-laden macrophages, AMRF do not show these. We studied fate relation deficiency employing recently designed...
Background: Sporadic Parkinson's disease (PD) patients have lower ␣-galactosidase A (␣-GAL A) enzymatic activity and Fabry (FD) potentially carry an increased risk of PD.Objective: Determination PD prevalence in FD clinical, biochemical vascular neuroimaging description pedigrees with concomitant PD.
Lysosomal storage disorders (LSDs) are a group of rare inherited metabolic diseases caused by the malfunction lysosomal system, which results in accumulation undergraded substrates inside lysosomes and leads to severe progressive pathology. Despite there currently being broad understanding molecular defects behind LSDs, curative therapies have been approved for only few these diseases, whereas existing treatments still mostly symptomatic with several limitations. Mucolipidosis type II...
Fabry disease (FD) is a treatable cause of hypertrophic cardiomyopathy (HCM). We aimed to determine the independent predictors FD and define clinically useful strategy discriminate among HCM.Multicenter study including 780 patients with ESC definition HCM. screening was performed by enzymatic assay in males genetic testing females. Multivariate regression analysis identified A discriminant function defined score based on weighted combination these predictors.FD found 37 HCM (4.7%): 31...
Among the many Lysosomal Storage Disorders (LSDs) that would benefit from establish-ment of novel cell models, either patient-derived or genetically engineered, is Mucopolysaccha-ridosis type II (MPS II). In fact, even though a specific therapeutic approach does exist for this disorder (Enzyme Replacement Therapy, ERT, with recombinant human IDS) and haematopoiet-ic stem transplantation (HSCT) may also hold promise whenever diagnosed soon enough, both approaches have their own...
Among the many lysosomal storage disorders (LSDs) that would benefit from establishment of novel cell models, either patient-derived or genetically engineered, is mucopolysaccharidosis type II (MPS II). Here, we present our results on and characterization two MPS stem line(s) deciduous baby teeth. To best knowledge, this first time a population has been isolated LSD patient samples obtained dental pulp. Taking into account molecular biochemical those cells fact they exhibit visible...
We report on the clinical, biochemical, and genetic findings of a large family with classical phenotype Fabry disease due to novel nonsense mutation c.607G>T (p.E203X) <i>GLA</i> gene, which occurs in active site α-galactosidase A enzyme. This highlights that (i) diagnosis should be considered all cases unexplained left ventricular hypertrophy (LVH), even its milder forms; (ii) complete evaluation patients LVH is important find diagnostic red flags treatable causes LVH, such...
When it comes to disease modeling, countless models are available for Lysosomal Storage Diseases (LSD). Historically, two major approaches well-established: in vitro assessments performed patient fibroblasts, while vivo pre-clinical studies mouse models. Still, both platforms have a series of drawbacks. Thus, we implemented alternative and innovative protocols mimic particular sub-group LSDs, the Mucopolysaccharidoses vivo.The first one relies on non-invasive approach using dental pulp stem...
The genetic variation at a compound nonrecombining haplotype system, consisting of the previously reported SB19.3 Alu insertion polymorphism and newly identified adjacent short tandem repeat (STR), was studied in population samples from Portugal São Tomé (Gulf Guinea, West Africa). Age estimates based on linked microsatellite suggest that occurred about 190,000 years ago. In accordance with global patterns distribution human variation, highest diversity found African sample. This excess due...