A5075146018- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- Trace Elements in Health
- Alzheimer's disease research and treatments
- RNA regulation and disease
- Metabolism and Genetic Disorders
- RNA Research and Splicing
- Nuclear Structure and Function
- Amino Acid Enzymes and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Advanced Chemical Physics Studies
- Mitochondrial Function and Pathology
- Bacteriophages and microbial interactions
- Neonatal Health and Biochemistry
- Gas Sensing Nanomaterials and Sensors
- Growth Hormone and Insulin-like Growth Factors
- Animal Genetics and Reproduction
- Biotin and Related Studies
- Sperm and Testicular Function
- Chemical and Physical Properties of Materials
- Polyamine Metabolism and Applications
- Crystal Structures and Properties
- Pain Management and Placebo Effect
- High-pressure geophysics and materials
- Transition Metal Oxide Nanomaterials
University of Alberta
2012-2022
Virologie et Immunologie Moléculaires
2007
Institut de Pharmacologie Moléculaire et Cellulaire
2003-2004
Centre National de la Recherche Scientifique
1977-2004
Istituto Superiore di Sanità
2003
Washington University in St. Louis
1997-1998
Inserm
1996-1998
University of Southern California
1996
Université de Bordeaux
1996
NutriNeuro
1996
The electronic band structure of titanium dioxide is calculated by a combined tight-binding and pseudopotential method in order to interpret the numerous experimental data. gap anisotropy clearly shown values parallel perpendicular gaps are good agreement with measured ones.
The physiological environment which hosts the conformational conversion of cellular prion protein (PrP(C)) to disease-associated isoforms has remained enigmatic. A quantitative investigation PrP(C) interactome was conducted in a cell culture model permissive replication. To facilitate recognition relevant interactors, study extended Doppel (Prnd) and Shadoo (Sprn), two mammalian paralogs. Interestingly, this work not only established similar for three family members neuroblastoma cells, but...
Transmission of chronic wasting disease (CWD) between cervids is influenced by the primary structure host cellular prion protein (PrP(C)). In white-tailed deer, PRNP alleles encode polymorphisms Q95 G96 (wild type [wt]), S96 (referred to as allele), and H95 which differentially impact CWD progression. We hypothesize that transmission prions deer expressing different allotypes PrP(C) modifies contagious agent affecting spread. To evaluate properties derived experimentally from four genotypes...
Development of transmissible spongiform encephalopathies (TSEs) pathogenesis requires the presence both normal host prion protein (PrP-sen) and abnormal pathological proteinase-K resistant isoform (PrP-res). PrP-res forms highly insoluble aggregates, with self-perpetuating properties, by binding converting PrP-sen molecules into a likeness themselves. In present report, we show that small interfering RNA (siRNA) duplexes trigger specific Prnp gene silencing in scrapie-infected neuroblastoma...
The Sprn gene encodes Shadoo (Sho), a glycoprotein with biochemical properties similar to the unstructured region of cellular prion protein (PrP C ). Sho has been considered candidate for hypothetical π that supplies PrP -like function maintain viability Prnp 0/0 mice lacking protein. To understand these relationships more clearly we probed cell biology and created knockout mice. Besides full-length “C1” C-terminal fragment, describe 6-kDa N-terminal neuropeptide, “N1,” which is present in...
The central causative event in infectious, familial, and sporadic forms of prion disease is thought to be a conformational change that converts the cellular isoform protein (PrPC) into scrapie (PrPSc) primary constituent infectious particles. To provide model system for analyzing mechanistic details this critical transformation, we have previously prepared cultured Chinese hamster ovary cells stably express mouse PrP molecules carrying mutations homologous those seen familial diseases...
It has been shown previously that ovine prion protein (PrP(C)) renders rabbit epithelial RK13 cells permissive to the multiplication of prions, thus providing evidence species barriers can be crossed in cultured through expression a relevant PrP(C). The present study significantly extended this observation by showing mouse and bank vole prions propagated express corresponding Importantly, respective molecular patterns abnormal PrP (PrP(res)) and, where examined, neuropathological features...
The electronic band structures of magnesium and calcium oxides are calculated by a combined tight-binding pseudopotential method; we show the possibility having two excitonic transitions in CaO one MgO, which is agreement with experimental results. We also propose an interpretation other
Genetic and biochemical mechanisms linking onset or progression of Alzheimer Disease prion diseases have been lacking and/or controversial, their etiologies are often considered independent. Here we document a novel, conserved specific genetic interaction between the proteins that underlie these diseases, amyloid-β precursor protein protein, APP PRP, respectively. Knockdown PRNP homologs in zebrafish (appa, appb, prp1, prp2) produces dose-dependent phenotype characterized by systemic...
Abstract Background The microtubule-associated protein tau forms aggregates in different neurodegenerative diseases called tauopathies. Prior work has shown that a single P301L mutation gene, MAPT , can promote alternative folding pathways correlate with divergent clinical diagnoses. Using progressive chemical denaturation, some preparations from the brain featured complex transitions starting at low concentrations of guanidine hydrochloride (GdnHCl) denaturant, indicating an ensemble...
During prion infections of the central nervous system (CNS) cellular protein, PrPC, is templated to a conformationally distinct form, PrPSc. Recent studies have demonstrated that Sprn gene encodes GPI-linked glycoprotein Shadoo (Sho), which localizes similar membrane environment as PrPC and reduced in brains rodents with terminal disease. Here, analyses prion-infected mice revealed down-regulation Sho protein was not related mRNA abundance at any stage infection. Down-regulation robust upon...
Abstract Tau protein accumulation is a common denominator of major dementias, but this process inhomogeneous, even when triggered by the same germline mutation. We considered stochastic misfolding human tau conformers followed templated conversion native monomers as an underlying mechanism and derived sensitive conformational assays to test concept. Assessments brains from aged TgTau P301L transgenic mice revealed prodromal state three distinct signatures for misfolded tau. Frontotemporal...
We have studied the interactions of exogenous prions with an epithelial cell line inducibly expressing PrPc protein and permissive to infection by a sheep scrapie agent. demonstrate that abnormal PrP (PrPSc) prion infectivity are efficiently internalized in Rov cells, whether or not is expressed. At odds earlier studies implicating cellular heparan sulfates PrPSc internalization, we failed find any involvement such molecules indicating can enter target cells several routes. further show...
J. Neurochem. (2010) 10.1111/j.1471‐4159.2010.06575.x Abstract The cellular prion protein PrP C refolds into a β‐sheet enriched, infectivity‐associated form called Sc . Shadoo (Sho) is newly discovered glycoprotein that also expressed in the adult brain. Wild type (wt) mouse Sho consists of an arginine‐rich region, hydrophobic central domain five tandem A/LAAG amino acid repeats R1–R5 with similarity to , and C‐terminal one N‐linked carbohydrate. As some alanine‐rich proteins shortened...
Prion diseases are characterized by conformational changes of a cellular prion protein (PrP(C)) into β-sheet-enriched and aggregated conformer (PrP(Sc)). Shadoo (Sho), member the family, is expressed in central nervous system (CNS) highly conserved among vertebrates. On basis histoanatomical colocalization sequence similarities, it suspected that Sho PrP may be functionally related. The downregulation expression during pathology direct interaction between PrP, as revealed two-hybrid...
To explore pathogenesis in a young Gerstmann-Sträussler-Scheinker Disease (GSS) patient, the corresponding mutation, an eight-residue duplication hydrophobic region (HR), was inserted into wild type mouse PrP gene. Transgenic (Tg) lines expressing this mutation (Tg.HRdup) developed spontaneous neurologic syndromes and brain extracts hastened disease low-expressor Tg.HRdup mice, suggesting de novo formation of prions. While mice exhibited spongiform change, aggregates anticipated GSS hallmark...
The physiological environment which hosts the conformational conversion of cellular prion protein (PrP C ) to diseaseassociated isoforms has remained enigmatic.A quantitative investigation PrP interactome was conducted in a cell culture model permissive replication.To facilitate recognition relevant interactors, study extended Doppel (Prnd) and Shadoo (Sprn), two mammalian paralogs.Interestingly, this work not only established similar for three family members neuroblastoma cells, but also...
MAPT mutations cause neurodegenerative diseases such as frontotemporal dementia but, strikingly, patients with the same mutation may have different clinical phenotypes.Given heterogeneities observed in a transgenic (Tg) mouse line expressing low levels of human (2 N, 4R) P301L Tau, we backcrossed founder stocks mice to C57BL/6Tac, 129/SvEvTac and FVB/NJ inbred backgrounds discern role genetic versus environmental effects on disease-related phenotypes.Three derivatives TgTauP301L had similar...
The cellular prion protein PrP(C) is encoded by the Prnp gene. This expressed in central nervous system (CNS) and serves as a precursor to misfolded PrP(Sc) isoform diseases. prototype disease scrapie sheep, whereas exhibits common missense polymorphisms for V136A, R154H Q171R ovine populations, genetic variation mouse limited. Recently CNS glycoprotein Shadoo (Sho) has been shown resemble both hydrophobic domain activity toxicity assay performed cerebellar neurons. Sho levels are reduced...