A5046924858- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- Trace Elements in Health
- Alzheimer's disease research and treatments
- RNA regulation and disease
- Alcoholism and Thiamine Deficiency
- Infectious Encephalopathies and Encephalitis
- Amino Acid Enzymes and Metabolism
- RNA Research and Splicing
- Neuroscience and Neuropharmacology Research
- Parkinson's Disease Mechanisms and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Biotin and Related Studies
- Amyotrophic Lateral Sclerosis Research
- Mitochondrial Function and Pathology
- Dementia and Cognitive Impairment Research
- Enzyme Structure and Function
- Multiple Sclerosis Research Studies
- Neurological disorders and treatments
- Nuclear Structure and Function
- Neurological Disorders and Treatments
- HIV Research and Treatment
- Cholinesterase and Neurodegenerative Diseases
- Proteins in Food Systems
- Bacteriophages and microbial interactions
Case Western Reserve University
2016-2025
University School
2015-2024
Sorbonne Université
2019-2020
Ikerbasque
2020
University of Zurich
2020
University Hospitals of Cleveland
2019
Centre National de la Recherche Scientifique
2019
Massachusetts General Hospital
2019
Harvard University
2019
Inserm
2019
The infectious isoform of the prion protein (PrPSc) is derived from cellular PrP (PrPC) in a conversion reaction involving dramatic reorganization secondary and tertiary structure. While our understanding pathogenic role PrPSc has grown, normal physiologic function PrPC still remains unclear. Using recombinant Syrian hamster [SHaPrP(29−231)], we investigated metal ions as possible ligands PrP. Near-UV circular dichroism spectroscopy (CD) indicates that conformation SHaPrP(29−231) resembles...
mation.Finally, if the PrPSc is only component of scrapie agent, it critical to understand its structure-function relationships.In this paper, we have compared following: ( a ) secondary structure infectious (biologically active) preparations and PrP27-30 reconstituted into liposomes; b conformational changes both proteins induced by assembly solid state in thin films; (c) transitions hamster protein during equilibrium dissociation unfolding GdnHCl.These characteristics were assayed circular...
The diagnosis and treatment of synucleinopathies such as Parkinson disease dementia with Lewy bodies would be aided by the availability assays for pathogenic disease-associated forms α-synuclein (αSyn
Accumulation of phosphorylated tau is a key pathological feature Alzheimer's disease. Phosphorylated accumulation causes synaptic impairment, neuronal dysfunction and formation neurofibrillary tangles. The actions are mediated by surrounding proteins; however, comprehensive understanding the proteins that interacts with in disease surprisingly limited. Therefore, aim this study was to determine interactome. To end, we used two complementary proteomics approaches: (i) quantitative performed...
Objective Several prion amplification systems have been proposed for detection of prions in cerebrospinal fluid (CSF), most recently, the measurements seeding activity with second‐generation real‐time quaking‐induced conversion (RT‐QuIC). The objective this study was to investigate diagnostic performance RT‐QuIC test broad phenotypic spectrum diseases. Methods We performed CSF testing 2,141 patients who had rapidly progressive neurological disorders, determined sensitivity and specificity...
Abstract Prion disease is a fatal neurodegenerative caused by the misfolding of prion protein (PrP) encoded PRNP gene. While there currently no cure for disease, depleting PrP in brain an established strategy to prevent or stall templated PrP. Here we developed vivo cytosine and adenine base strategies delivered adeno-associated viruses permanently modify locus achieve knockdown mouse brain. Systemic injection dual-adeno-associated virus PHP.eB encoding BE3.9max single guide RNA installing...
With the discovery of prion protein (PrP), immunodiagnostic procedures were applied to diagnose Creutzfeldt–Jakob disease (CJD). Before development conformation-dependent immunoassay (CDI), all immunoassays for disease-causing PrP isoform (PrP Sc ) used limited proteolysis digest precursor cellular C ). Because CDI is only that measures both protease-resistant and protease-sensitive forms , we human disease. The gave a positive signal in 10–24 brain regions (100%) examined from 28 CJD...
ABSTRACT Branched polyamines, including polyamidoamine and polypropyleneimine (PPI) dendrimers, are able to purge PrP Sc , the disease-causing isoform of prion protein, from scrapie-infected neuroblastoma (ScN2a) cells in culture (S. Supattapone, H.-O. B. Nguyen, F. E. Cohen, S. Prusiner, M. R. Scott, Proc. Natl. Acad. Sci. USA 96:14529–14534, 1999). We now demonstrate that exposure ScN2a 3 μg PPI generation 4.0/ml for 4 weeks not only reduced a level undetectable by Western blot but also...
Abstract The scrapie amyloid (prion) protein (PrP27–30) is the protease‐resistant core of a larger precursor (PrP Sc ) and component infectious agent; potential to form result posttranslational event or conformational abnormality. conformation, heat stability, solvent‐induced transitions PrP27–30 were studied in solid state films by CD spectroscopy correlated with infectivity rehydrated equilibrated films. exposure 60 °C, 100 132 °C for 30 min did not change β ‐sheet secondary structure;...
Chronic wasting disease (CWD) is a fatal prion in deer and elk. Unique among the diseases, it transmitted captive free-ranging animals. To facilitate studies of biology CWD prions, we generated five lines transgenic (Tg) mice expressing protein (PrP) from Rocky Mountain elk (Cervus elaphus nelsoni), denoted Tg(ElkPrP), two Tg PrP common to white-tailed (Odocoileus virginianus) mule hemionus), Tg(DePrP). None Tg(ElkPrP) or Tg(DePrP) exhibited spontaneous neurologic dysfunction at more than...
Genetic and environmental factors that increase the risk of late-onset Alzheimer disease are now well recognized but cause variable progression rates phenotypes sporadic Alzheimer's is largely unknown. We aimed to investigate relationship between diverse structural assemblies amyloid-β clinical decline in disease. Using novel biophysical methods, we analysed levels, particle size, conformational characteristics posterior cingulate cortex, hippocampus cerebellum 48 cases with distinctly...
In chronic wasting disease (CWD) in cervids and scrapie sheep, prions appear to be transmitted horizontally. Oral exposure prion-tainted blood, urine, saliva, feces has been suggested as the mode of transmission CWD among herbivores susceptible these prion diseases. To explore through feces, uninoculated Syrian hamsters (SHas) were cohabitated with or exposed bedding SHas orally infected Sc237 prions. Incubation times 140 days a rate infection 80%-100% animals by probably via coprophagy. We...
Five phenotypically distinct subtypes have been identified in sporadic Creutzfeldt–Jakob disease (sCJD), based on the methionine/valine polymorphic genotype of codon 129 prion protein (PrP) gene and presence either one two protease K-resistant scrapie (PrPSc) types as 1 2. The infrequent co-existence both PrPSc same case has known for a long time. Recently, it reported, using type-specific antibodies, that type is present all cases sCJD carrying consistent co-occurrence complicates diagnosis...
Infectious prions can be detected in the skin of patients with sporadic Creutzfeldt-Jakob disease.
The presence of pathology related to the deposition amyloid-β (Aβ) has been recently reported in iatrogenic Creutzfeldt-Jakob disease (iCJD) acquired from inoculation growth hormone (GH) extracted human cadaveric pituitary gland or use dura mater (DM) grafts. To investigate this phenomenon further, a cohort 27 iCJD cases – 21 with adequate number histopathological sections originating Australia, France, Italy, and Unites States, were examined by immunohistochemistry, amyloid staining,...
To determine whether preventive trials in genetic prion disease could be designed to follow presymptomatic mutation carriers onset of disease.We assembled age at or death data from 1,094 individuals with high penetrance mutations the protein gene (PRNP) order generate survival and hazard curves test for modifiers onset. We used formulae simulations estimate statistical power clinical trials.Genetic varies over several decades most common neither sex, parent's onset, nor PRNP codon 129...
Recent progress determining the structure of host-encoded prion protein (PrP C ) and role auxiliary molecules in replication permits a more rational approach development therapeutic interventions. Our objective is to identify new class lead compounds that mimic dominant negative PrP mutants, which inhibit an abnormal isoform Sc formation. A computational search was conducted on Available Chemicals Directory for both spatial orientation basic polymorphism residues 168, 172, 215, 219, confer...
There is considerable concern that bovine prions from cattle with spongiform encephalopathy (BSE) may have been passed to humans (Hu), resulting in a new form of Creutzfeldt–Jakob disease (CJD). We report here the transmission (Bo) transgenic (Tg) mice expressing BoPrP; one Tg line exhibited incubation times ≈200 days. Like most BSE, vacuolation and astrocytic gliosis were confined brainstems these mice. Unexpectedly, chimeric Bo/Mo PrP transgene resistant BSE whereas Hu or Hu/Mo transgenes...
Our discovery of dominant-negative inhibition prion formation in cultured cells provided an explanation for the resistance some sheep to scrapie and humans Creutzfeldt–Jakob disease. To determine whether occurs vivo , we produced transgenic (Tg) mice expressing protein (PrP) with either Q167R or Q218K mutation alone combination wild-type (wt) PrP. Tg(MoPrP,Q167R) Prnp 0/0 mutant PrP at levels equal non-Tg remained healthy >550 days, indicating that inoculation prions did not cause...