Mouse Brain Synaptosomes Accumulate Copper-67 Efficiently by Two Distinct Processes Independent of Cellular Prion Protein

2005 ◽  
Vol 27 (3) ◽  
pp. 347-354 ◽  
Author(s):  
Armin Giese ◽  
Malte Buchholz ◽  
Jochen Herms ◽  
Hans A. Kretzschmar
Keyword(s):  
Prion Protein ◽  
Mouse Brain ◽  
Cellular Prion Protein ◽  
Brain Synaptosomes

Differential expression of cellular prion protein in mouse brain as detected with multiple anti-PrP monoclonal antibodies

2001 ◽  
Vol 896 (1-2) ◽  
pp. 118-129 ◽  
Author(s):  
Tong Liu ◽  
Theresa Zwingman ◽  
Ruliang Li ◽  
Tao Pan ◽  
Boon-Seng Wong ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Differential Expression ◽  
Prion Protein ◽  
Mouse Brain ◽  
Cellular Prion Protein

scholarly journals Highly infectious prions are not directly neurotoxic

2020 ◽  
Vol 117 (38) ◽  
pp. 23815-23822 ◽  
Author(s):  
Iryna Benilova ◽  
Madeleine Reilly ◽  
Cassandra Terry ◽  
Adam Wenborn ◽  
Christian Schmidt ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Prion Protein ◽  
Mouse Brain ◽  
High Titer ◽  
Cellular Prion Protein ◽  
Cultured Neurons ◽  
Direct Test ◽  
Infectious Agents ◽  
Incubation Periods ◽  
Prion Propagation

Prions are infectious agents which cause rapidly lethal neurodegenerative diseases in humans and animals following long, clinically silent incubation periods. They are composed of multichain assemblies of misfolded cellular prion protein. While it has long been assumed that prions are themselves neurotoxic, recent development of methods to obtain exceptionally pure prions from mouse brain with maintained strain characteristics, and in which defined structures—paired rod-like double helical fibers—can be definitively correlated with infectivity, allowed a direct test of this assertion. Here we report that while brain homogenates from symptomatic prion-infected mice are highly toxic to cultured neurons, exceptionally pure intact high-titer infectious prions are not directly neurotoxic. We further show that treatment of brain homogenates from prion-infected mice with sodium lauroylsarcosine destroys toxicity without diminishing infectivity. This is consistent with models in which prion propagation and toxicity can be mechanistically uncoupled.

scholarly journals Pharmacological inactivation of the prion protein by targeting a folding intermediate

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Giovanni Spagnolli ◽  
Tania Massignan ◽  
Andrea Astolfi ◽  
Silvia Biggi ◽  
Marta Rigoli ◽  
...  
Keyword(s):  
Prion Protein ◽  
Prion Diseases ◽  
Cellular Prion Protein ◽  
Surface Glycoprotein ◽  
Folding Intermediate ◽  
Biological Regulation ◽  
Cell Surface Glycoprotein ◽  
Folding Intermediates ◽  
Protein Levels ◽  
Small Molecule Ligands

AbstractRecent computational advancements in the simulation of biochemical processes allow investigating the mechanisms involved in protein regulation with realistic physics-based models, at an atomistic level of resolution. These techniques allowed us to design a drug discovery approach, named Pharmacological Protein Inactivation by Folding Intermediate Targeting (PPI-FIT), based on the rationale of negatively regulating protein levels by targeting folding intermediates. Here, PPI-FIT was tested for the first time on the cellular prion protein (PrP), a cell surface glycoprotein playing a key role in fatal and transmissible neurodegenerative pathologies known as prion diseases. We predicted the all-atom structure of an intermediate appearing along the folding pathway of PrP and identified four different small molecule ligands for this conformer, all capable of selectively lowering the load of the protein by promoting its degradation. Our data support the notion that the level of target proteins could be modulated by acting on their folding pathways, implying a previously unappreciated role for folding intermediates in the biological regulation of protein expression.

Peptide NMHRYPNQ of the Cellular Prion Protein (PrPC) Inhibits Aggregation and Is a Potential Key for Understanding Prion–Prion Interactions

2009 ◽  
Vol 392 (1) ◽  
pp. 198-207 ◽  
Author(s):  
Dirk Rehders ◽  
Birgit Claasen ◽  
Lars Redecke ◽  
Alexander Buschke ◽  
Caroline Reibe ◽  
...  
Keyword(s):  
Prion Protein ◽  
Cellular Prion Protein

Cellular prion protein acquires resistance to proteolytic degradation following copper ion binding

2004 ◽  
Vol 385 (8) ◽  
Author(s):  
Thorsten Kuczius ◽  
Anne Buschmann ◽  
Wenlan Zhang ◽  
Helge Karch ◽  
Karsten Becker ◽  
...  
Keyword(s):  
Prion Protein ◽  
Copper Ion ◽  
Cellular Prion Protein ◽  
Proteolytic Degradation ◽  
Ion Binding
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