A5062931258- Prion Diseases and Protein Misfolding
- Trace Elements in Health
- Neurological diseases and metabolism
- Enzyme Structure and Function
- Alzheimer's disease research and treatments
- Diet and metabolism studies
- Amino Acid Enzymes and Metabolism
- RNA regulation and disease
- Monoclonal and Polyclonal Antibodies Research
- Adipose Tissue and Metabolism
- Infectious Encephalopathies and Encephalitis
- RNA Research and Splicing
- HIV Research and Treatment
- Porphyrin Metabolism and Disorders
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Bacteriophages and microbial interactions
- Metabolism and Genetic Disorders
- Diet, Metabolism, and Disease
- Nutritional Studies and Diet
- Metabolomics and Mass Spectrometry Studies
- Circadian rhythm and melatonin
- Computational Drug Discovery Methods
- CRISPR and Genetic Engineering
- Inflammasome and immune disorders
- Muscle metabolism and nutrition
University Hospital of Zurich
2011-2024
University of Zurich
2015-2024
D’Or Institute for Research and Education
2024
Sorbonne Université
2020
Ikerbasque
2020
German Institute of Human Nutrition
2013-2019
German Center for Diabetes Research
2018
Heinrich Heine University Düsseldorf
2018
Deutsches Diabetes-Zentrum e.V.
2018
ETH Zurich
1999-2014
The recombinant murine prion protein, m PrP(23–231), was expressed in E. coli with uniform 15 N‐labeling. NMR experiments showed that the previously determined globular three‐dimensional structure of C‐terminal domain PrP(121–231) is preserved intact and N‐terminal polypeptide segment 23–120 flexibly disordered. This structural information based on nearly complete sequence‐specific assignments for backbone amide nitrogens, protons α‐protons residues 121–231 PrP(23–231). Coincidence...
The prion protein is known to be a copper-binding protein, but affinity and stoichiometry data for the full-length at physiological pH of 7 were lacking. Furthermore, it was unknown whether only highly flexible N-terminal segment with its octarepeat region involved in copper binding or structured C-terminal domain also involved. Therefore we systematically investigated PrP23–231 different N- fragments using electrospray ionization mass spectrometry fluorescence spectroscopy. Our indicate...
The infectious agent of transmissible spongiform encephalopathies is believed to consist an oligomeric isoform, PrPSc, the monomeric cellular prion protein, PrPC. conversion PrPC PrPSc characterized by a decrease in alpha-helical structure, increase beta-sheet content, and formation amyloid. Whereas N-terminal part comprising residues 23-120 flexibly disordered, its C-terminal part, PrP(121-231), forms globular domain with three alpha-helices small beta-sheet. Because segment 90-231...
The refined NMR structure of the mouse prion protein domain m PrP(121–231) and recently reported complete 208-residue polypeptide chain PrP are used to investigate structural basis inherited human transmissible spongiform encephalopathies. In cellular form no spatial clustering mutation sites is observed that would indicate existence disease-specific subdomains. A hydrogen bond between residues 128 178 provides a for highly specific influence polymorphism in position 129 on disease phenotype...
By immunizing prion knockout mice (Prnp-/-) with recombinant murine protein (PrPc), we obtained a panel of mAbs specific for PrPc. These can be applied to immunoblotting, cell surface immunofluorescent staining, and immunohistochemistry at light electron microscopy. recognize both the normal (PrPc) protease-resistant (PrPres) isoforms PrP. Some are species restricted, while others react PrP from broad range mammals including mice, humans, monkeys, cows, sheep, squirrels, hamsters. Moreover,...
The cellular prion protein of the mouse, m PrP C , consists 208 amino acids (residues 23–231). It contains a carboxy‐terminal domain, PrP(121–231), which represents an autonomous folding unit with three α‐helices and two‐stranded antiparallel β‐sheet. We expressed complete acid sequence protein, PrP(23–231), in cytoplasm Escherichia coli . PrP(23–231) was solubilized from inclusion bodies by 8 M urea, oxidatively refolded purified to homogeneity conventional chromatographic techniques....
Most transmissible spongiform encephalopathies arise either spontaneously or by infection. Mutations of PRNP, which encodes the prion protein, PrP, segregate with phenotypically similar diseases. Here we report that moderate overexpression in transgenic mice mPrP(170N,174T), a mouse PrP two point mutations subtly affect structure its globular domain, causes fully penetrant lethal encephalopathy cerebral plaques. This genetic disease was reproduced 100% attack rate intracerebral inoculation...
PrPSc, a misfolded and aggregated form of the cellular prion protein PrPC, is only defined constituent transmissible agent causing diseases. Expression PrPC in host organism necessary for replication neurotoxicity. Understanding diseases necessitates detailed structural insights into PrPSc. Towards this goal, we have developed comprehensive collection monoclonal antibodies denoted POM1 to POM19 directed against many different epitopes mouse PrPC. Three are located within N-terminal...
The analytical "gold standard" for amyloid characterization and diagnostics, Congo red, was studied in complex with an (see picture). Based on details of the binding mode, a point mutation prepared which has same three-dimensional structure as wild-type protein but is not congophilic. This surprising specificity may aid design selective anti-amyloidogenic drugs. Detailed facts importance to specialist readers are published "Supporting Information". Such documents peer-reviewed, copy-edited...
Transmissible spongiform encephalopathies are lethal neurodegenerative disorders that present with aggregated forms of the cellular prion protein (PrPC), which known as PrPSc. Prions from different species vary considerably in their transmissibility to xenogeneic hosts. The variable transmission barriers depend on sequence differences between incoming PrPSc and host PrPC additionally, strain-dependent conformational properties β2-α2 loop region within varies substantially species, its...
The targeted chemical design of luminescent conjugated polythiophenes may yield new therapeutic compounds for treating prion diseases.
Article26 July 2021Open Access Source DataTransparent process LAG3 is not expressed in human and murine neurons does modulate α-synucleinopathies Marc Emmenegger orcid.org/0000-0002-6073-8811 Institute of Neuropathology, University Zurich, Switzerland These authors contributed equally to this work Search for more papers by author Elena De Cecco orcid.org/0000-0002-0148-2596 Marian Hruska-Plochan orcid.org/0000-0002-9253-4362 Department Quantitative Biomedicine, Timo Eninger German Center...
The structural basis of species specificity transmissible spongiform encephalopathies, such as bovine encephalopathy or “mad cow disease” and Creutzfeldt–Jakob disease in humans, has been investigated using the refined NMR structure C-terminal domain mouse prion protein with residues 121–231. A database search for mammalian proteins yielded 23 different sequences fragment 124–226, which display a high degree sequence identity show relevant amino acid substitutions only 18 103 positions....
Prions induce lethal neurodegeneration and consist of PrPSc, an aggregated conformer the cellular prion protein PrPC. Antibody-derived ligands to globular domain PrPC (collectively termed GDL) are also neurotoxic. Here we show that GDL infections activate same pathways. Firstly, both infection cerebellar organotypic cultured slices (COCS) induced production reactive oxygen species (ROS). Accordingly, ROS scavenging, which counteracts toxicity in vitro vivo, prolonged lifespan prion-infected...
Protein misfolding into amyloid-like aggregates underlies many neurodegenerative diseases. Thus, insights the structure and function of these amyloids will provide valuable information on pathological mechanisms involved aid in design improved drugs for treating amyloid-based disorders. However, determining endogenous at high resolution has been difficult. Here we employ binding-activated localization microscopy (BALM) to acquire superresolution images α-synuclein amyloid fibrils with...
Primary Familial Brain Calcification (PFBC), a neurodegenerative disease characterized by progressive pericapillary calcifications, has recently been linked to heterozygous mutations in PDGFB and PDGFRB genes. Here, we functionally analyzed several of these vitro. All six led complete loss PDGF-B function either through abolished protein synthesis or defective binding and/or stimulation PDGF-Rβ. The three had more diverse consequences. Whereas PDGF-Rβ autophosphorylation was almost totally...
Zoonotic prion transmission was reported after the bovine spongiform encephalopathy (BSE) epidemic, when >200 cases of disease in humans were diagnosed as variant Creutzfeldt-Jakob disease. Assessing risk cross-species remains challenging. We and others have studied how specific amino acid residue differences between species impact conversion found that β2-α2 loop region mouse protein (residues 165–175) markedly influences infection by sheep scrapie, BSE, mouse-adapted deer chronic...