Article
Multidisciplinary Sciences
Angela Chong, James D. Foster, Wilfred Goldmann, Lorenzo Gonzalez, Martin Jeffrey, Matthew J. O'Connor, Keith Bishop, Ben C. Maddison, E. Fiona Houston, Kevin C. Gough, Nora Hunter
Summary: The study reports on mixed-prion infections in sheep with bovine spongiform encephalopathy (BSE) and scrapie. The results showed that VRQ/ARQ sheep challenged with mixed infections developed scrapie-like incubation periods, while VRQ/VRQ sheep challenged with BSE showed scrapie-like incubation periods.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Adelaida Hernaiz, Sara Sentre, Marina Betancor, Oscar Lopez-Perez, Monica Salinas-Pena, Pilar Zaragoza, Juan Jose Badiola, Janne Markus Toivonen, Rosa Bolea, Inmaculada Martin-Burriel
Summary: Scrapie is a transmissible spongiform encephalopathy characterized by the presence of the abnormal prion protein PrPSc. This study investigates the involvement of DNA methylation in scrapie pathogenesis by analyzing the levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in infected brain tissues of sheep and mice. The results show a decrease in 5mC levels and opposite patterns of 5hmC between the two models. Additionally, expression analysis of epigenetic regulatory genes reveals differences between the disease models. These findings support the role of DNA methylation and associated enzymes in the neurodegenerative course of prion diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Hiroki Otaki, Yuzuru Taguchi, Noriyuki Nishida
Summary: This article investigates the relationship between the conformation of PrPSc and hydrophobic amino acids, and finds that subtle differences between these amino acids can greatly affect the stability of PrPSc structures.
Article
Biotechnology & Applied Microbiology
Kathryn S. Beauchemin, Judy R. Rees, Surachai Supattapone
Summary: Alternating regimens using different classes of anti-prion drugs reduce the incidence of drug-resistant strains but do not significantly increase long-term disease-free survival in scrapie-infected mice. The emergence of strain dominance may be induced by alternating regimens.
JOURNAL OF GENERAL VIROLOGY
(2021)
Article
Clinical Neurology
Simone Baiardi, Angela Mammana, Sofia Dellavalle, Marcello Rossi, Veronica Redaelli, Elisa Colaizzo, Giuseppe Di Fede, Anna Ladogana, Sabina Capellari, Piero Parchi
Summary: The study systematically characterized the clinical and histo-molecular features of the MV2 subtype with kuru plaques in Creutzfeldt-Jakob disease. They evaluated the neurological histories, biomarkers, MRI and EEG results of 126 patients and found that the MV2K subtype has distinct features, including a longer disease duration, prominent cerebellar symptoms, and positive cerebrospinal fluid tests. The use of real-time quaking-induced conversion assay and brain diffusion-weighted MRI can improve early clinical diagnosis in most patients.
Article
Biochemistry & Molecular Biology
Savroop Bhamra, Parineeta Arora, Szymon W. Manka, Christian Schmidt, Craig Brown, Melissa L. D. Rayner, Peter-Christian Klohn, Anthony R. Clarke, John Collinge, Parmjit S. Jat, Louise C. Serpell
Summary: The N-terminal residues within PrPC, specifically amino acids 105-111 in CC2, are necessary for the propagation of four different mouse prion strains. These residues mediate the ordering of unstructured CC2 into infectious prion fibrils.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Neurosciences
James F. Striebel, Brent Race, Jacqueline M. Leung, Cindi Schwartz, Bruce Chesebro
Summary: Accumulation of misfolded host proteins, like PrPSc, in the retina during prion infection leads to early damage to the inner segments of photoreceptor cells and eventual death. Neurons in the outer plexiform layer are selectively targeted by prion deposition, with loss of ribbon synapses preceding widespread destruction of rods and cones.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Sophie Mouillet-Richard, Severine Martin-Lanneree, Delphine Le Corre, Theo Z. Hirsch, Alexandre Ghazi, Marine Sroussi, Camilla Pilati, Aurelien de Reynies, Fatima Djouadi, Nicolas Vodovar, Jean-Marie Launay, Pierre Laurent-Puig
Summary: The cellular prion protein PrPC and caveolin-1 (CAV1) have been found to interact in neurodegenerative diseases and cancer. This study uncovers the molecular link between PrPC and CAV1 in cancer, showing that PrPC regulates CAV1 expression and interacts with it. PrPC also controls the expression of other proteins related to Alzheimer's disease and regulates the levels of A beta.
Article
Chemistry, Multidisciplinary
Dillan Stengel, J. Bennett Addison, David Onofrei, Nha Uyen Huynh, George Youssef, Gregory P. Holland
Summary: This study revealed the unique water-induced cross-linking mechanism in orb-weaving spider aciniform silk, increasing the beta-sheet content and stiffness of the silk. Mechanical shear further enhances beta-sheet cross-linking, resulting in 4-6 nm beta-sheet domains. The observation of converting a flexible alpha-helix-rich fiber to a rigid beta-sheet mat through water treatment may open new possibilities in bioinspired materials design.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Neurosciences
Ying Xia, Cao Chen, Jia Chen, Chao Hu, Wei Yang, Lin Wang, Lian Liu, Li-Ping Gao, Yue-Zhang Wu, Dong-Dong Chen, Qi Shi, Zhi-Bao Chen, Xiao-Ping Dong
Summary: This study found that the M-CSF/IL-34/CSF1R signaling pathway is activated in prion infection and plays a crucial role in the pathophysiology of prions. Inhibiting M-CSF/CSF1R signaling may have therapeutic potential for prion diseases.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Neurosciences
Qin Fan, Kang Xiao, A. Ruhan, Li-Ping Gao, Yue-Zhang Wu, Dong-Dong Chen, Chao Hu, Xiao-Xi Jia, Chu-Mou Liu, Xin Liu, Cao Chen, Qi Shi, Xiao-Ping Dong
Summary: Mitochondrial dysfunction and metabolic dysfunctions contribute to the progression of prion disease. The key enzymes in the glycolysis pathway are increased while the mitochondrial complexes are downregulated in prion-infected models. Clearance of prion propagation partially reverses these alterations, indicating a metabolic reprogramming from oxidative phosphorylation to glycolysis.
MOLECULAR NEUROBIOLOGY
(2023)
Review
Cell Biology
Waqas Tahir, Simrika Thapa, Hermann M. Schatzl
Summary: Prion diseases are infectious protein misfolding disorders that affect the central nervous system. The role of astrocytes, non-neuronal cells in the brain, in prion pathogenesis is complex and not fully understood. Astrocytes can regulate brain homeostasis, but they can also deposit and propagate prions. However, the exact role of astrocytes in prion diseases and the lack of in vitro models limit our understanding and research in this area.
NEURAL REGENERATION RESEARCH
(2022)
Article
Biochemical Research Methods
Truc Lam Pham, Michael Kovermann, Franziska Thomas
Summary: This study presents a monomeric beta-sheet peptide that can switch between a molten globule and folded state through Zn(II) binding, with specific recognition of Zn(II) compared to other divalent metal ions. The peptide is pH-switchable, surviving multiple cycles of acidification and neutralization. Structural characterization was achieved through circular dichroism and multinuclear NMR spectroscopy, indicating a viable approach for a globular beta-sheet Zn(II) mini-receptor prototype.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Nanoscience & Nanotechnology
Emma Olson, Justin S. Plaut, Sarah A. Barnhill, Sinan Sabuncu, Corey M. Dambacher, Sean D. Speese, Srivathsan Ranganathan, Bruce P. Branchaud, Adem Yildirim
Summary: A sensitive method for detecting protease activity using a beta-sheet-rich nanoplatelet-forming peptide precursor and thioflavin T has been developed, allowing for detection of specific proteases like legumain. This method shows promise for various protease-detection applications due to its simplicity and low cost, and does not require time-consuming conjugation reactions or purification steps.
ACS APPLIED NANO MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Kenta Teruya, Sara Iwabuchi, Yuki Watanabe, Rikiya Tsuchida, Miki Watanabe-Matsui, Hiroyuki Konno, Katsumi Doh-ura
Summary: This study treated persistently prion-infected cells with curcumin-related compounds and found that the compounds had different effects on cells infected with different prion strains. Chemometric analysis was used to determine the factors contributing to these effects, showing that different molecular properties were responsible for the reduction of PrPSc levels in one cell line and the formation of PrPSc dimers in another.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2022)
Article
Biophysics
Sylwia Czarnota, Nicola J. Baxter, Matthew J. Cliff, Jonathan P. Waltho, Nigel S. Scrutton, Sam Hay
BIOMOLECULAR NMR ASSIGNMENTS
(2017)
Article
Biochemistry & Molecular Biology
Pavel Macek, Matthew J. Cliff, Kevin J. Embrey, Geoffrey A. Holdgate, J. Willem M. Nissink, Stanislava Panova, Jonathan P. Waltho, Rick A. Davies
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Chemistry, Physical
Luke A. Johnson, Angus J. Robertson, Nicola J. Baxter, Clare R. Trevitt, Claudine Bisson, Yi Jin, Henry P. Wood, Andrea M. Hounslow, Matthew J. Cliff, G. Michael Blackburn, Matthew W. Bowler, Jonathan P. Waltho
Article
Chemistry, Physical
Andreea I. Iorgu, Nicola J. Baxter, Matthew J. Cliff, Colin Levy, Jonathan P. Waltho, Sam Hay, Nigel S. Scrutton
Article
Chemistry, Physical
Sylwia Czarnota, Linus O. Johannissen, Nicola J. Baxter, Felix Rummel, Alex L. Wilson, Matthew J. Cliff, Colin W. Levy, Nigel S. Scrutton, Jonathan P. Waltho, Sam Hay
Article
Biophysics
F. Aaron Cruz-Navarrete, Nicola J. Baxter, Henry P. Wood, Andrea M. Hounslow, Jonathan P. Waltho
BIOMOLECULAR NMR ASSIGNMENTS
(2019)
Article
Biochemistry & Molecular Biology
Stanislava Panova, Matthew J. Cliff, Pavel Macek, Martin Blackledge, Malene Ringkjobing Jensen, J. Willem M. Nissink, Kevin J. Embrey, Rick Davies, Jonathan P. Waltho
Article
Chemistry, Multidisciplinary
Alex L. Wilson, Carlos Outeiral, Sarah E. Dowd, Andrew J. Doig, Paul L. A. Popelier, Jonathan P. Waltho, Andrew Almond
COMMUNICATIONS CHEMISTRY
(2020)
Article
Biology
Laszlo L. P. Hosszu, Rebecca Conners, Daljit Sangar, Mark Batchelor, Elizabeth B. Sawyer, Stuart Fisher, Matthew J. Cliff, Andrea M. Hounslow, Katherine McAuley, R. Leo Brady, Graham S. Jackson, Jan Bieschke, Jonathan P. Waltho, John Collinge
COMMUNICATIONS BIOLOGY
(2020)
Article
Chemistry, Physical
Angus J. Robertson, F. Aaron Cruz-Navarrete, Henry P. Wood, Nikita Vekaria, Andrea M. Hounslow, Claudine Bisson, Matthew J. Cliff, Nicola J. Baxter, Jonathan P. Waltho
Summary: Understanding the factors contributing to the high catalytic efficiencies of enzymes is crucial for catalysis and enzyme design. This study investigates the relationship between binding a phosphodianion group in a distal site, adopting a closed enzyme form, and catalytic proficiency. The results suggest that binding of a phosphodianion group in the distal site stimulates domain closure and stabilizes the closed active form, leading to high catalytic efficiencies.
Article
Chemistry, Physical
Angus J. Robertson, Alex L. Wilson, Matthew J. Burn, Matthew J. Cliff, Paul L. A. Popelier, Jonathan P. Waltho
Summary: The study using QM models, experimental NMR measurements, and X-ray structures revealed that the transition of an archetypal phosphoryl transfer enzyme, beta PGM, triggers partial proton transfer and partial dissociation of phosphoryl group. Proton transfer continues but is not completed during the reaction with the enzyme in the TSA conformation. Changes in proton position and electrostatic repulsion stimulate phosphoryl transfer.
Article
Biochemistry & Molecular Biology
Laszlo L. P. Hosszu, Daljit Sangar, Mark Batchelor, Emmanuel Risse, Andrea M. Hounslow, John Collinge, Jonathan P. Waltho, Jan Bieschke
Summary: In prion replication, the conversion of cellular form of prion protein (PrPC) to its disease-associated fibrillar form is achieved through a full conformational transition. Transmembrane forms of PrP play a role in this structural conversion. Removing residues 119-136 of PrP, which includes the first β-strand and a large portion of the conserved hydrophobic region associated with the ER membrane, resulted in an open native-like conformer of PrPC with increased solvent exposure and enhanced fibril formation. These findings suggest a stepwise folding transition initiated by the conformational switch to this open form of PrPC.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Henry P. Wood, Nicola J. Baxter, F. Aaron Cruz-Navarrete, Clare R. Trevitt, Andrea M. Hounslow, Jonathan P. Waltho
Summary: The study demonstrated an efficient enzymatic synthesis method for anomer-specific beta G16BP using the D170N variant of beta PGM. The perturbation of catalytic magnesium ion coordination by the substitution at residue 170 in the enzyme was found to contribute to the accumulation of beta G16BP. The purification process employed a simple and environmentally friendly precipitation procedure, resulting in a high purity and yield of the beta G16BP product.
Article
Multidisciplinary Sciences
Henry P. Wood, F. Aaron Cruz-Navarrete, Nicola J. Baxter, Clare R. Trevitt, Angus J. Robertson, Samuel R. Dix, Andrea M. Hounslow, Matthew J. Cliff, Jonathan P. Waltho
NATURE COMMUNICATIONS
(2020)
Article
Biophysics
Andreea I. Iorgu, Nicola J. Baxter, Matthew J. Cliff, Jonathan P. Waltho, Sam Hay, Nigel S. Scrutton
BIOMOLECULAR NMR ASSIGNMENTS
(2018)