Adriano Aguzzi
University of Zurich
TransgeneGeneGenetically modified mousePathologyMolecular biologyVirologyAntibodyNeuroscienceChemistryImmunologyScrapieNeurodegenerationPRNPDiseasePathogenesisPrion proteinGeneticsMedicineBiologyCell biology
692Publications
132H-index
47.2kCitations
Publications 662
Newest
#1Manfredi Carta (UZH: University of Zurich)H-Index: 2
#2Adriano Aguzzi (UZH: University of Zurich)H-Index: 132
Despite being caused by a single protein, prion diseases are strikingly heterogenous. Individual prion variants, known as strains, possess distinct biochemical properties, form aggregates with characteristic morphologies and preferentially seed certain brain regions, causing markedly different disease phenotypes. Strain diversity is determined by protein structure, post-translational modifications and the presence of extracellular matrix components, with single amino acid substitutions or altere...
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#1Karl Frontzek (UZH: University of Zurich)H-Index: 11
#2Marco Bardelli (USI: University of Lugano)H-Index: 9
Last. Georg Meisl (University of Cambridge)H-Index: 27
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Summary null Prion infections cause conformational changes of PrPC and lead to progressive neurological impairment. Here we show that toxic, prion-mimetic ligands induce an intramolecular R208-H140 hydrogen bond (“H-latch”) altering the flexibility of the α2-α3 and β2-α2 loops of PrPC. Expression of a PrP2Cys mutant mimicking the H-latch was constitutively toxic, whereas a PrPR207A mutant unable to form the H-latch conferred resistance to prion infection. High-affinity ligands that prevented H-l...
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#1Caihong Zhu (Fudan University)H-Index: 9
#2Adriano Aguzzi (UZH: University of Zurich)H-Index: 132
Prion diseases are neurodegenerative disorders caused by conformational conversion of the cellular prion protein (PrPC) into scrapie prion protein (PrPSc). As the main component of prion, PrPSc acts as an infectious template that recruits and converts normal cellular PrPC into its pathogenic, misfolded isoform. Intriguingly, the phenomenon of prionoid, or prion-like, spread has also been observed in many other disease-associated proteins, such as amyloid β (Aβ), tau and α-synuclein. This Cell Sc...
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1 CitationsSource
#1Sebastian FiedlerH-Index: 14
#2Viola DenningerH-Index: 8
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Understanding the factors that contribute to antibody escape of SARS-CoV-2 and its variants is key for the development of drugs and vaccines that provide broad protection against a variety of virus variants. Using microfluidic diffusional sizing, we determined the dissociation constant (KD) for the interaction between receptor binding domains (RBDs) of SARS-CoV-2 in its original version (WT) as well as alpha and beta variants with the host-cell receptor angiotensin converting enzyme 2 (ACE2). Fo...
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#1Viola DenningerH-Index: 8
#2Catherine K. Xu (University of Cambridge)H-Index: 9
Last. Matthias Schneider (University of Cambridge)H-Index: 14
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Recent efforts in understanding the course and severity of SARS-CoV-2 infections have highlighted both potential beneficial as well as detrimental effects of cross-reactive antibodies derived from memory immunity. Specifically, due to a significant degree of sequence similarity between SARS-CoV-2 and other members of the coronavirus family, memory B-cells that emerged from previous infections with endemic human coronaviruses (HCoVs) could be re-activated upon encountering the newly emerged SARS-...
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#1Asvin K. K. Lakkaraju (UZH: University of Zurich)H-Index: 7
#2Karl Frontzek (UZH: University of Zurich)H-Index: 11
Last. Adriano Aguzzi (UZH: University of Zurich)H-Index: 132
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Brain-matter vacuolation is a defining trait of all prion diseases, yet its cause is unknown. Here, we report that prion infection and prion-mimetic antibodies deplete the phosphoinositide kinase PIKfyve-which controls endolysosomal maturation-from mouse brains, cultured cells, organotypic brain slices, and brains of Creutzfeldt-Jakob disease victims. We found that PIKfyve is acylated by the acyltransferases zDHHC9 and zDHHC21, whose juxtavesicular topology is disturbed by prion infection, resul...
1 CitationsSource
#1Daniel Kirschenbaum (UZH: University of Zurich)H-Index: 7
#2Fabian F. Voigt (UZH: University of Zurich)H-Index: 12
Last. Paolo Paganetti (USI: University of Lugano)H-Index: 44
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Genetic and biochemical evidence implicates amyloid-β (Aβ) in Alzheimer9s disease, yet many anti-Aβ treatments are clinically ineffective. Regional heterogeneity of efficacy may contribute to these disappointing results. Here we mapped the regiospecificity of various anti-Aβ treatments by high-resolution light-sheet imaging of amyloid plaques in electrophoretically clarified brains of Thy1-APP mice overexpressing Aβ. We found that Aβ plaques in whole brains progressed from 1.2*106 to 2.5*106 (st...
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#5Thomas BuettnerH-Index: 2
#7Peter Schierack (BTU: Brandenburg University of Technology)H-Index: 25
Last. Adriano Aguzzi (UZH: University of Zurich)H-Index: 132
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Antiphospholipid antibodies (aPL), assumed to cause antiphospholipid syndrome (APS), are notorious for their heterogeneity and detect phospholipids and phospholipid-binding proteins. The persistent presence of Lupus anticoagulant and/or aPL against cardiolipin and/or {beta}2 glycoprotein I have been shown to be independent risk factors for vascular thrombosis and pregnancy morbidity in APS. Among others, viral infections have been proposed to trigger the production of aPL while mostly being cons...
3 CitationsSource
Neuropathological and experimental evidence suggests that the cell-to-cell transfer of α-synuclein has an important role in the pathogenesis of Parkinson's disease (PD). However, the mechanism underlying this phenomenon is not fully understood. We undertook a small interfering RNA (siRNA), genome-wide screen to identify genes regulating the cell-to-cell transfer of α-synuclein. A genetically encoded reporter, GFP-2A-αSynuclein-RFP, suitable for separating donor and recipient cells, was transient...
1 CitationsSource