A5032728621- Prion Diseases and Protein Misfolding
- Neurological diseases and metabolism
- Trace Elements in Health
- RNA regulation and disease
- ATP Synthase and ATPases Research
- Mitochondrial Function and Pathology
- Alzheimer's disease research and treatments
- Monoclonal and Polyclonal Antibodies Research
- Biotin and Related Studies
- Photosynthetic Processes and Mechanisms
- Amino Acid Enzymes and Metabolism
- Cellular transport and secretion
- Infectious Encephalopathies and Encephalitis
- Lipid Membrane Structure and Behavior
- RNA modifications and cancer
- Animal Genetics and Reproduction
- Neurobiology and Insect Physiology Research
- RNA Research and Splicing
- Biochemical effects in animals
- Metabolism and Genetic Disorders
- RNA and protein synthesis mechanisms
- Viral Infectious Diseases and Gene Expression in Insects
- Cardiomyopathy and Myosin Studies
- Bacterial biofilms and quorum sensing
- Erythrocyte Function and Pathophysiology
University of Oxford
1990-2025
Boston University
2014-2024
Virginia Tech
2024
Friedrich-Alexander-Universität Erlangen-Nürnberg
2024
University School
2012-2017
Laboratoire de Biochimie
2013
Dartmouth College
2012
Scripps Research Institute
2009-2012
The University of Melbourne
2011
Washington University in St. Louis
2001-2010
Prion diseases result from conformational alteration of PrPC, a cell surface glycoprotein expressed in brain, spinal cord, and several peripheral tissues, into PrPSc, protease-resistant isoform that is the principal component infectious prion particles. Although great deal known about pathogenic role physiological function PrPC has remained mystery. Several lines evidence have recently suggested possibility PrPCmay play metabolism copper. To further investigate interaction copper, we...
Generation of reactive oxygen species (ROS), leading to oxidative damage and neuronal cell death, plays an important role in the pathogenesis neurodegenerative disorders, including Alzheimer disease. The present study aimed examine mechanism by which anti-aging protein Klotho exerts neuroprotective effects against associated with neurodegeneration stress. Pretreatment rat primary hippocampal neurons mouse line HT22 recombinant protected these cells from glutamate oligomeric amyloid β...
It has been known for a number of years that glycosyl-phosphatidylinositol (GPI)-anchored proteins, in contrast to many transmembrane are insoluble at 4 degrees C nonionic detergents such as Triton X-100. Recently, it proposed this behavior reflects the incorporation GPI-linked proteins into large aggregates rich sphingolipids and cholesterol, well cytoplasmic signaling molecules heterotrimeric G src-family tyrosine kinases. suggested these lipid-protein complexes derived from caveolae,...
The prion protein (PrPC) is a glycolipid-anchored, cell surface of unknown function, posttranslationally modified isoform which has been implicated in the pathogenesis spongiform encephalopathies man and animals. We report here novel observation that chPrP, chicken homologue mammalian PrPC, constitutively cycles between an endocytic compartment with transit time approximately 60 min, as demonstrated by iodination immunofluorescence microscopy. Most (> 95%) internalized returned to intact,...
The cellular prion protein (PrPc) is a glycolipid-anchored, cell surface of unknown function, posttranslationally modified isoform which PrPSc involved in the pathogenesis Creutzfeldt-Jakob disease, scrapie, and other spongiform encephalopathies. We have shown previously that chPrP, chicken homologue mammalian PrPC, constitutively cycles between an endocytic compartment, with transit time approximately 60 min cultured neuroblastoma cells. now report endocytosis chPrP mediated by...
ABSTRACT Propagation of the agents responsible for transmissible spongiform encephalopathies (TSEs) in cultured cells has been achieved only a few cell lines. To establish efficient and versatile models transmission, we developed neuroblastoma lines overexpressing type A mouse prion protein, MoPrP C -A, then tested susceptibility to several different mouse-adapted scrapie strains. The transfected clones expressed up sixfold-higher levels PrP than untransfected cells. Even after 30 passages,...
The cellular mechanisms by which prions cause neurological dysfunction are poorly understood. To address this issue, we have been using cultured cells to analyze the localization, biosynthesis, and metabolism of PrP molecules carrying mutations associated with familial prion diseases. We report here that mutant delayed in their maturation an endoglycosidase H-resistant form after biosynthetic labeling, suggesting they impaired exit from endoplasmic reticulum (ER). However, find proteasome...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProcessing of a cellular prion protein: identification N- and C-terminal cleavage sitesDavid A. Harris, Mary T. Huber, Peter Van Dijken, Show Ling Shyng, Brian Chait, Rong WangCite this: Biochemistry 1993, 32, 4, 1009–1016Publication Date (Print):February 1, 1993Publication History Published online1 May 2002Published inissue 1 February 1993https://pubs.acs.org/doi/10.1021/bi00055a003https://doi.org/10.1021/bi00055a003research-articleACS...
Prion diseases are neurodegenerative disorders that result from conformational transformation of a normal cell surface glycoprotein, PrP<sup>C</sup>, into pathogenic isoform, PrP<sup>Sc</sup>. Although the physiological function PrP<sup>C</sup> has remained enigmatic, recent observation protein binds copper ions with micromolar affinity suggests possible role in brain metabolism. In this study, we have used mice express 0, 1, and 10 times level PrP to assess effect expression on amount...
A hallmark of Alzheimer disease (AD) is the accumulation amyloid-β (Aβ) peptide in brain. Considerable evidence suggests that soluble Aβ oligomers are responsible for synaptic dysfunction and cognitive deficit observed AD. However, mechanism by which these exert their neurotoxic effect remains unknown. Recently, it was reported bind to cellular prion protein with high affinity. Here, we show N1, main physiological cleavage fragment protein, necessary sufficient binding early oligomeric...
Neurodegenerative diseases are an enormous public health problem, affecting tens of millions people worldwide. Nearly all these characterized by oligomerization and fibrillization neuronal proteins, there is great interest in therapeutic targeting aggregates. Here, we show that soluble aggregates α-synuclein tau bind to plate-immobilized PrP vitro on mouse cortical neurons, this binding requires at least one the same N-terminal sites which Aβ bind. Moreover, tau, cause both functional...
The cellular prion protein (PrPC) is a glycolipid-anchored that involved in the pathogenesis of fatal spongiform encephalopathies. We have shown previously that, contrast to several other proteins, chPrP, chicken homologue mammalian PrPC, endocytosed via clathrin-coated pits cultured neuroblastoma cells, as well embryonic neurons and glia (Shyng, S.-L., Heuser, J. E., Harris, D. A.(1994) Cell Biol. 125, 1239-1250). In this study, we determined N-terminal half chPrP polypeptide chain...
Several lines of evidence have suggested that copper ions play a role in the biology both PrPC and PrPSc, normal pathologic forms prion protein. To further investigate this intriguing connection, we analyzed how affect biochemical properties extracted from brains transgenic mice transfected cells. We report metal rapidly reversibly induces to become protease-resistant detergent-insoluble. Although these two are commonly associated with demonstrate using conformation-dependent immunoassay...
The conformational conversion of the prion protein, a sialoglycoprotein containing two N-linked oligosaccharide chains, from its normal form (PrPC) to pathogenic (PrPSc) is central causative event in diseases. Although PrPSc can be generated absence glycosylation, there evidence that chains may modulate efficiency process, and also serve as molecular markers diverse strains. In addition, mutational inactivation one N-glycosylation sites has recently been associated with familial spongiform...