A5065182658- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- Trace Elements in Health
- RNA regulation and disease
- Plant Virus Research Studies
- Microtubule and mitosis dynamics
- Glioma Diagnosis and Treatment
- Cell death mechanisms and regulation
- Amino Acid Enzymes and Metabolism
- Plant Disease Resistance and Genetics
- Plant and Fungal Interactions Research
- Alcoholism and Thiamine Deficiency
- Monoclonal and Polyclonal Antibodies Research
- DNA Repair Mechanisms
- Immunotherapy and Immune Responses
- Animal Genetics and Reproduction
- Telomeres, Telomerase, and Senescence
- Advanced Algorithms and Applications
- Biotin and Related Studies
- Synthesis of Tetrazole Derivatives
- Alzheimer's disease research and treatments
- Advanced Sensor and Control Systems
- Industrial Technology and Control Systems
- Mitochondrial Function and Pathology
- T-cell and B-cell Immunology
Case Western Reserve University
2015-2024
University School
2010-2023
MRC Prion Unit
2014-2019
Neurology, Inc
2019
University Hospitals of Cleveland
2017
University Hospitals Cleveland Medical Center
2015
Taishan Medical University
2015
Center for Environmental Health
2003-2014
Institut du Cerveau
2013
Inserm
2013
Abstract Objective To report a novel prion disease characterized by distinct histopathological and immunostaining features, associated with an abnormal isoform of the protein (PrP) that, contrary to common diseases, is predominantly sensitive protease digestion. Methods Eleven subjects were investigated at National Prion Disease Pathology Surveillance Center for clinical, histopathological, immunohistochemical, genotypical, PrP characteristics. Results Patients presented behavioral...
Abstract Objective: The objective of the study is to report 2 new genotypic forms protease‐sensitive prionopathy (PSPr), a novel prion disease described in 2008, 11 subjects all homozygous for valine at codon 129 protein (PrP) gene (129VV). PSPr affect individuals who are either methionine (129MM) or heterozygous methionine/valine (129MV). Methods: Fifteen affected with 129MM, 129MV, and 129VV underwent comparative evaluation National Prion Disease Pathology Surveillance Center clinical,...
Chronic wasting disease (CWD), a prion affecting free-ranging and captive cervids (deer elk), is widespread in the United States parts of Canada. The large cervid population, popularity venison consumption, apparent spread CWD epidemic are likely resulting increased human exposure to States. Whether transmissible humans, as has been shown for bovine spongiform encephalopathy (the cattle), unknown. We generated transgenic mice expressing elk or protein (PrP) PrP-null background. After...
Bovine spongiform encephalopathy (BSE), the prion disease in cattle, was widely believed to be caused by only one strain, BSE-C. BSE-C causes fatal named new variant Creutzfeldt-Jacob humans. Two atypical BSE strains, bovine amyloidotic (BASE, also BSE-L) and BSE-H, have been discovered several countries since 2004; their transmissibility phenotypes humans are unknown. We investigated infectivity human phenotype of BASE strains inoculating transgenic (Tg) mice expressing protein with brain...
Infectious prions can be detected in the skin of patients with sporadic Creutzfeldt-Jakob disease.
Aggregated prion protein (PrPSc), which is detergent-insoluble and partially proteinase K (PK)-resistant, constitutes the major component of infectious prions that cause a group transmissible spongiform encephalopathies in animals humans. PrPSc derives from detergent-soluble PK-sensitive cellular (PrPC) through an α-helix to β-sheet transition. This transition confers on molecule unique physicochemical biological properties, including insolubility nondenaturing detergents, enhanced tendency...
Despite overwhelming evidence implicating the prion protein (PrP) in disease pathogenesis, normal function of this cell surface glycoprotein remains unclear. In previous reports we demonstrated that PrP mediates cellular iron uptake and transport, aggregation to causing PrP-scrapie (PrP(Sc)) form results imbalance homeostasis affected human animal brains. Here, show selective deletion transgenic mice (PrP(KO)) alters systemic as reflected hematological parameters levels total regulatory...
The mammalian prions replicate by converting cellular prion protein (PrPC) into pathogenic conformational isoform (PrPSc). Variations in prions, which cause different disease phenotypes, are referred to as strains. mechanism of high-fidelity replication strains the absence nucleic acid remains unsolved. We investigated impact characteristics PrPSc on conversion PrPC vitro using seeds from most frequent human worldwide, Creutzfeldt-Jakob (sCJD). potency a broad spectrum distinct sCJD was...
Chronic wasting disease (CWD) is a fatal prion of North American deer and elk poses an unclear risk for transmission to humans. Human exposure CWD occurs through hunting activities consumption venison from prion-infected animals. Although the amino acid residues protein (PrP) that prevent or permit human infection are unknown, NMR-based structural studies suggest β2-α2 loop (residues 165-175) may impact species barriers. Here we sought define PrP sequence determinants affect We engineered...
Significance Prion diseases are a group of transmissible neurodegenerative disorders. The protein-only hypothesis asserts that transmission these does not require nucleic acids and misfolded, aggregated form the prion protein represents self-perpetuating infectious agent. Even though this model is supported by large body experimental data, there dispute regarding role specific cofactors in infectivity as well structural basis formation. In work, we show structurally well-characterized...
The symptoms of prion infection can take years or decades to manifest following the initial exposure. Molecular markers disease include accumulation misfolded protein (PrPSc), which is derived from its cellular precursor (PrPC), as well downregulation PrP-like Shadoo (Sho) glycoprotein. Given overlapping environments for PrPC and Sho, we inferred that levels might also be altered part a host response during infection. Using rodent models, found that, in addition changes glycosylation...
Neurotoxicity in all prion disorders is believed to result from the accumulation of PrP-scrapie (PrP(Sc)), a beta-sheet rich isoform normal cell-surface glycoprotein, protein (PrP(C)). Limited reports suggest imbalance brain iron homeostasis as significant associated cause neurotoxicity prion-infected cell and mouse models. However, systematic studies on generality this phenomenon underlying mechanism(s) leading dyshomeostasis diseased brains are lacking. In report, we demonstrate that...
Abstract A definitive pre-mortem diagnosis of prion disease depends on brain biopsy for detection currently and no validated alternative preclinical diagnostic tests have been reported to date. To determine the feasibility using skin diagnosis, here we report ultrasensitive serial protein misfolding cyclic amplification (sPMCA) real-time quaking-induced conversion (RT-QuIC) assays samples from hamsters humanized transgenic mice (Tg40h) at different time points after intracerebral inoculation...
Abstract Chronic wasting disease (CWD) is a cervid prion caused by the accumulation of an infectious misfolded conformer (PrP Sc ) cellular protein C ). It has been spreading rapidly in North America and also found Asia Europe. Although bovine spongiform encephalopathy (i.e. mad cow disease) only animal known to be zoonotic, transmissibility CWD humans remains uncertain. Here we report generation first CWD-derived human PrP elk -seeded conversion normal brain homogenates using vitro...
The principal infectious and pathogenic agent in all prion disorders is a β-sheet–rich isoform of the cellular protein (PrP C ) termed PrP-scrapie Sc ). Once initiated, PrP self-replicating toxic to neuronal cells, but underlying mechanisms remain unclear. In this report, we demonstrate that binds iron transforms -like form (*PrP when human neuroblastoma cells are exposed an inorganic source redox iron. *PrP thus generated itself active, it induces transformation additional , simulating...
The epitope of the 3F4 antibody most commonly used in human prion disease diagnosis is believed to consist residues Met-Lys-His-Met (MKHM) corresponding PrP-(109-112). This assumption based mainly on observation that reacts with and hamster PrP but not from mouse, sheep, cervids, which Met at residue 112 replaced by Val. Here we report that, brain histoblotting, did react uninfected transgenic mice expressing elk PrP; however, it show distinct immunoreactivity infected chronic wasting...
The unique phenotypic characteristics of mammalian prions are thought to be encoded in the conformation pathogenic prion proteins (PrP(Sc)). molecular mechanism responsible for adaptation, mutation, and evolution observed cloned cells upon crossing species barrier remains unsolved. Using biophysical techniques conformation-dependent immunoassays tandem, we isolated two distinct populations PrP(Sc) particles with different conformational stabilities aggregate sizes, which frequently co-exist...
Abstract Variably protease-sensitive prionopathy (VPSPr), a recently identified and seemingly sporadic human prion disease, is distinct from Creutzfeldt-Jakob disease (CJD) but shares features of Gerstmann-Sträussler-Scheinker (GSS). However, contrary to exclusively inherited GSS, no protein (PrP) gene variations have been detected in VPSPr, suggesting that VPSPr might be the long-sought form GSS. The atypical raised issue transmissibility, prototypical property diseases. We inoculated brain...