A5049008682- Lysosomal Storage Disorders Research
- Glycosylation and Glycoproteins Research
- Cellular transport and secretion
- Calcium signaling and nucleotide metabolism
- Glycogen Storage Diseases and Myoclonus
- Carbohydrate Chemistry and Synthesis
- Chromatin Remodeling and Cancer
- Biomedical Research and Pathophysiology
- Alzheimer's disease research and treatments
- Retinal Development and Disorders
- Genomics and Chromatin Dynamics
- Atherosclerosis and Cardiovascular Diseases
- Galectins and Cancer Biology
- Cholesterol and Lipid Metabolism
- Peroxisome Proliferator-Activated Receptors
- Trypanosoma species research and implications
- Bone and Dental Protein Studies
- interferon and immune responses
- Hormonal Regulation and Hypertension
- Neurological diseases and metabolism
- Pharmacological Effects of Natural Compounds
- Vitamin C and Antioxidants Research
- Advanced Glycation End Products research
- Neonatal and fetal brain pathology
- Ocular Surface and Contact Lens
Centre Hospitalier Universitaire Sainte-Justine
2014-2025
Université de Montréal
2013-2024
Shandong Academy of Sciences
2021-2022
Qilu University of Technology
2021-2022
Dongguan People’s Hospital
2013
Dalhousie University
2011
Changchun Normal University
2005-2007
Northeast Normal University
2005-2007
The removal of sialic acid (Sia) residues from glycoconjugates in vertebrates is mediated by a family neuraminidases (sialidases) consisting Neu1, Neu2, Neu3 and Neu4 enzymes. enzymes play distinct physiological roles, but their ability to discriminate between the types linkages connecting Sia adjacent identity arrangement underlying sugars has never been systematically studied. Here we analyzed specificity studying kinetics hydrolysis BODIPY-labeled substrates containing common mammalian...
Neuraminidases (sialidases) catalyze the removal of sialic acid residues from sialylated glycoconjugates. We now report that mammalian neuraminidase 1 (Neu1), in addition to its catabolic function lysosomes, is transported cell surface where it involved regulation insulin signaling. Insulin binding receptor rapidly induces interaction with Neu1, which hydrolyzes glycan chains and, consequently, activation. Cells sialidosis patients a genetic deficiency Neu1 show impairment insulin-induced...
Neuraminidase 1 (NEU1) cleaves terminal sialic acids of glycoconjugates during lysosomal catabolism. It also modulates the structure and activity cellular surface receptors affecting diverse pathways. Previously we demonstrated that NEU1 activates insulin receptor (IR) NEU1-deficient CathAS190A-Neo mice (hypomorph activator protein, cathepsin A/CathA) on a high-fat diet (HFD) develop hyperglycaemia resistance faster than wild-type animals. The major objective current work was to reveal...
Background Chronic vascular disease atherosclerosis starts with an uptake of atherogenic modified low-density lipoproteins (LDLs) by resident macrophages, resulting in formation arterial fatty streaks and eventually atheromatous plaques. Increased plasma sialic acid levels, increased neuraminidase activity, reduced LDL content have been previously associated coronary artery human patients, but the mechanism underlying this association has not explored. Methods Results We tested hypothesis...
Gangliosides (sialylated glycolipids) play an essential role in the CNS by regulating recognition and signaling neurons. Metabolic blocks processing catabolism of gangliosides result development severe neurologic disorders, including gangliosidoses manifesting with neurodegeneration neuroinflammation. We demonstrate that 2 mammalian enzymes, neuraminidases 3 4, important roles catabolic brain cleaving terminal sialic acid residues their glycan chains. In neuraminidase 4 double-knockout mice,...
The majority of mucopolysaccharidosis IIIC (MPS IIIC) patients have missense variants causing misfolding heparan sulfate acetyl-CoA:α-glucosaminide N-acetyltransferase (HGSNAT), which are potentially treatable with pharmacological chaperones. To test this approach, we generated a novel HgsnatP304L mouse model expressing misfolded HGSNAT Pro304Leu variant. mice present deficits in short-term and working/spatial memory 2-4 mo earlier than previously described constitutive knockout Hgsnat-Geo...
Neuronal accumulation of amyloid aggregates is a hallmark brain pathology in neurological lysosomal storage diseases (LSDs) including mucopolysaccharidoses (MPS), however, the molecular mechanism underlying this has not been understood. We demonstrate that elevated cathepsin B (CTSB) levels and CTSB leakage to cytoplasm triggers amyloidogenesis two LSDs. were 3-5-fold cortices mouse models MPS IIIC ( Hgsnat-Geo Hgsnat P304L ) sialidosis Neu1 ΔEx3 ), as well cortical samples I, IIIA, IIID...
Neuronal accumulation of amyloid aggregates is a hallmark brain pathology in neurological lysosomal storage diseases (LSDs), including mucopolysaccharidoses (MPS); however, the molecular mechanism underlying this has not been understood. We demonstrate that elevated cathepsin B (CTSB) levels and CTSB leakage to cytoplasm triggers amyloidogenesis two LSDs. were 3- 5-fold cortices mouse models MPS IIIC (Hgsnat-Geo Hgsnat P304L ) sialidosis (Neu1 ΔEx3 ), as well cortical samples I, IIIA, IIIC,...
Sialic acids are important components of glycoproteins and glycolipids essential for cellular communication, infection, metastasis. The importance sialic acid biosynthesis in human physiology is well illustrated by the severe metabolic disorders this pathway. However, biological role catabolism humans remains unclear. Here, we present evidence that heart skeletal muscle function development zebrafish. In two siblings, presenting with sialuria, exercise intolerance/muscle wasting, cardiac...
Mucopolysaccharidosis III type C (MPS IIIC) is an untreatable neuropathic lysosomal storage disease caused by a genetic deficiency of the N-acetyltransferase, HGSNAT, catalyzing transmembrane acetylation heparan sulfate. HGSNAT enzyme incapable free diffusion between cells or their cross-correction, which limits development therapies based on replacement and gene correction. Since our previous work identified neuroinflammation as hallmark CNS pathology in MPS IIIC, we tested whether it can...
The majority of patients affected with lysosomal storage disorders (LSD) exhibit neurological symptoms. For mucopolysaccharidosis type IIIC (MPSIIIC), the major burdens are progressive and severe neuropsychiatric problems dementia, primarily thought to stem from neurodegeneration. Using MPSIIIC mouse model, we studied whether clinical manifestations preceding massive neurodegeneration arise synaptic dysfunction. Reduced levels or abnormal distribution multiple proteins were revealed in...
Caffeic acid has been indicated to benefit cholesterol balance, but the effect of pure caffeic on atherosclerosis in vivo not tested. Given that and Alzheimer's disease share common features including distracted lipid balance chronic inflammation, concurrent effects atherosclerotic lesions cognitive decline were explored here by using ApoE-/- mice model. A two months' administration 20 mg/kg or saline was given once days intraperitoneally 5-month-old female mice. We found treatment reduced...
Atherogenesis is a long-term process that involves inflammatory response coupled with metabolic dysfunction. Foam cell formation and macrophage are two key events in atherogenesis. Adipocyte enhancer-binding protein 1 (AEBP1) has been shown to impede cholesterol efflux, promoting foam formation, via peroxisome proliferator-activated receptor (PPAR)-γl liver X α (LXRα) downregulation. Moreover, AEBP1 promote responsiveness by inducing nuclear factor (NF)-κB activity IκBα Lipopolysaccharide...
The potent vasoconstrictor peptides, endothelin 1 (ET-1) and angiotensin II control adaptation of blood vessels to fluctuations pressure. Previously we have shown that the circulating level ET-1 is regulated through its proteolytic cleavage by secreted serine carboxypeptidase, cathepsin A (CathA). However, genetically-modified mouse expressing catalytically inactive CathA S190A mutant retained about 10–15% carboxypeptidase activity against in tissues suggesting a presence parallel/redundant...
Deleterious variants in N- acetylneuraminate pyruvate lyase (NPL) cause skeletal myopathy and cardiac edema humans zebrafish, but its physiological role remains unknown. We report generation of mouse models the disease: Npl R63C , carrying human p.Arg63Cys variant, del116 with a 116-bp exonic deletion. In both strains, NPL deficiency causes drastic increase free sialic acid levels, reduction muscle force endurance, slower healing smaller size newly formed myofibers after cardiotoxin-induced...
The central molecular event underlying prion diseases involves conformational change of the cellular form protein (PrPC), which is a sialoglycoprotein, into disease-associated, transmissible denoted PrPSc. Recent studies revealed correlation between sialylation status PrPSc and incubation time to disease introduced new hypothesis that progression could be controlled or reversed by altering level PrPC. Of four known mammalian sialidases, enzymes cleave off sialic acid residues, only NEU1,...
Sialidosis is an ultra-rare multisystemic lysosomal disease caused by mutations in the neuraminidase 1 (NEU1) gene. The severe type II form of manifests with a prenatal/infantile or juvenile onset, bone abnormalities, neuropathology, and visceromegaly. A subset these patients present nephrosialidosis, characterized abrupt onset fulminant glomerular nephropathy. We studied pathophysiological mechanism 2 NEU1-deficient mouse models, constitutive Neu1-knockout, Neu1ΔEx3, conditional...
Heterozygous mutations in the UBIAD1 gene cause Schnyder corneal dystrophy characterized by abnormal cholesterol and phospholipid deposits cornea. Ubiad1 protein was recently identified as Golgi prenyltransferase responsible for biosynthesis of vitamin K2 CoQ10, a key mitochondrial electron transport chain. Our study shows that silencing cultured human hepatocellular carcinoma cells causes dramatic morphological changes storage mitochondria, emphasizing an important role function.
Actin is an important protein in nucleus and has been implicated transcription, however, the mechanism of its function transcription still not clear. In this article, we studied role actin regulation human CSF1 gene transcription. Our results showed that nuclear stimulates activity promoter, augmenting requires formation chromatin Z-DNA structure. The ATP binding motifs are essential for regulating upon overexpression, there increase ATPase proteins. Further investigation revealed regulates...
Vasoactive and mitogenic peptide, endothelin-1 (ET-1) plays an important role in physiology of the ocular tissues by regulating growth corneal epithelial cells maintaining hemodynamics intraocular fluids. We have previously established that ET-1 can be degraded vivo two lysosomal/secreted serine carboxypeptidases, Cathepsin A (CathA) Serine Carboxypeptidase 1 (Scpep1) gene-targeted CathAS190A /Scpep1-/- mice, deficient CathA Scpep1 a prolonged half-life circulating associated with systemic...
Phyllanthus emblica L. has been used for the prevention of cardiovascular disease, but its mechanisms remain unclear. In this study, fluorescence imaging in Zebrafish was to screen phytomedicines effects on atherosclerosis development vivo. We found that an ethyl-acetate extract P. fruit (E-EA) proved highly effective reducing vascular monocyte infiltration. The E-EA also reduced cholesterol deposition fed a high-fat diet. vitro, suppressed net macrophages response oxidized LDL. Suppression...