A5083558247- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- Trace Elements in Health
- Alcoholism and Thiamine Deficiency
- RNA regulation and disease
- Folate and B Vitamins Research
- Alzheimer's disease research and treatments
- Lymphoma Diagnosis and Treatment
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Amyotrophic Lateral Sclerosis Research
- Celiac Disease Research and Management
- Microbial metabolism and enzyme function
- Cervical Cancer and HPV Research
- Biotin and Related Studies
- Metabolism and Genetic Disorders
- Renal Diseases and Glomerulopathies
- Amino Acid Enzymes and Metabolism
Case Western Reserve University
2015-2025
University School
2010-2025
National Center for Emerging and Zoonotic Infectious Diseases
2021
Centers for Disease Control and Prevention
2021
DePaul University
2018
University of Chicago
2018
Western University of Health Sciences
2018
University of Bologna
2018
Istituto delle Scienze Neurologiche di Bologna
2018
Istituto Superiore di Sanità
2018
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,...
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...
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...
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,...
Creutzfeldt-Jakob disease (CJD) is a rare, fatal, rapidly progressive neurodegenerative resulting from an accumulation of misfolded prion proteins (PrP). CJD affects 1-2 new individuals per million each year, and the sporadic type accounts for 90% those cases. Though median age at onset duration vary depending on subtype (sCJD), typically middle-aged to elderly with survival 4-6 months. sCJD in younger extremely rare. Here, we present 21-year-old female who died disease. She presented...
The sporadic form of Creutzfeldt-Jakob disease (sCJD) has been classified on the basis molecular mass protease-resistant scrapie prion protein (PrP(Sc)), which can be type 1 or 2, and genotype at methionine (M)/valine (V) polymorphic codon 129, MM, MV VV. In one classification proposed by Parchi et al., [Parchi P, Giese A, Capellari S, Brown Schulz-Schaeffer W, Windl O, Zerr I , Budka H Kopp N Piccardo P Poser S Rojiani A Streichemberger Julien J Vital C Ghetti B Gambetti Kretzschmar ....
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...
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...
Abstract The current classification of sporadic Creutzfeldt–Jakob disease (sCJD) includes six major clinicopathological subtypes defined by the physicochemical properties protease-resistant core pathologic prion protein (PrP Sc ), defining two PrP types (i.e., 1 and 2), methionine (M)/valine (V) polymorphic codon 129 gene ( PRNP ). How these sCJD relate to well-documented phenotypic heterogeneity genetic CJD (gCJD) is not fully understood. We analyzed molecular features in 208 individuals...
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...
Variant Creutzfeldt-Jakob disease (vCJD) is a prion thought to be acquired by the consumption of prion-contaminated beef products. To date, over 200 cases have been identified around world, but mainly in United Kingdom. Three States; however, these subjects were likely exposed infection elsewhere. Here we report on first subjects.Neuropathological and genetic examinations carried out using standard procedures. We assessed presence characteristics protease-resistant protein (PrP(res)) brain...
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...
A novel point mutation resulting in a glutamate-to-glycine substitution PRNP at codon 200, E200G with 129 MV polymorphism (cis valine) and type 2 PrPSc was identified patient prolonged disease course leading to pathology-proven Jakob-Creutzfeldt disease. Despite the same as most common genetic form of human mutation, E200K, this (E200G) presented different clinical pathological phenotype, including duration, large vacuoles, no vacuolation hippocampus, severe neuronal loss thalamus, mild...
The four glycoforms of the cellular prion protein (PrPC) variably glycosylated at two N-linked glycosylation sites are converted into their pathological forms (PrPSc) in most cases sporadic diseases. However, a prominent molecular characteristic PrPSc recently identified protease-sensitive prionopathy (VPSPr) is absence diglycosylated form, also notable familial Creutzfeldt-Jakob disease (fCJD), which linked to mutations PrP either from Val Ile residue 180 (fCJDV180I) or Thr Ala 183...
Variably protease-sensitive prionopathy (VPSPr), a recently described human sporadic prion disease, features protease-resistant, disease-related protein (resPrPD) displaying 5 fragments reminiscent of Gerstmann-Sträussler-Scheinker disease. Experimental VPSPr transmission to PrP-expressing transgenic mice, although replication the resPrPD profile succeeded, has been incomplete because second passage failure. We bioassayed in bank voles, which are susceptible strains. Transmission was...
Prion diseases, or transmissible spongiform encephalopathies (TSEs), are associated with the conformational conversion of cellular prion protein, PrPC, into a protease-resistant form, PrPSc. Here, we show that mutation-induced thermodynamic stabilization folded, α-helical domain PrPC has dramatic inhibitory effect on protein in vitro, as well propagation TSE disease vivo. Transgenic mice expressing human variant increased stability were found to be much more resistant infection agent than...
The occurrence of sporadic prion disease among adolescents is extremely rare. A was confirmed in an adolescent with onset at 13 years age. Genetic, neuropathologic, and biochemical analyses the patient's autopsy brain tissue were consistent fatal insomnia, a type disease. There no evidence environmental source infection, this patient represents youngest documented case Although rare, diagnosis should not be discounted exhibiting neurologic signs. Brain testing necessary for confirmation...
The present study compares the clinical, pathological and molecular features of a United States (US) case growth hormone (GH)-associated Creutzfeldt-Jakob disease (GH-CJD) (index case) to those two earlier referred US cases GH-CJD one dura mater (d)-associated CJD (dCJD). All iatrogenic (iCJD) subjects were methionine (M) homozygous at codon 129 (129MM) prion protein (PrP) gene had scrapie (PrPSc) type 1 (iCJDMM1). index subject presented with ataxia, weight loss changes in sleep pattern...
Abstract We report a detailed study of cohort sporadic Creutzfeldt-Jakob disease (sCJD) VV1–2 type-mixed cases (valine homozygosity at codon 129 the prion protein, PrP, gene harboring disease-related PrP D , types 1 and 2). Overall, sCJDVV1–2 subjects showed mixed clinical histopathological features, which often correlated with relative amounts corresponding type. However, type-specific phenotypic characteristics were only detected when amount type exceeded 20–25%. original features (T1) 2...
Background: Dominantly inherited Creutzfeldt-Jakob disease (CJD) represents 5% to 15% of all CJD cases.The E200K mutation in the prion protein (PrP) gene (PRNP) is most frequent cause familial CJD.Coexistent amyloid  (A) plaques have been reported some transmissible spongiform encephalopathies but date not with mutation.Objective: To characterize a family which A codistribute degeneration.Design: Clinicopathologic and molecular study E200K-129M haplotype.Setting: Alzheimer research...