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Real-time Quaking-induced Conversion Assay for Detection of CWD Prions in Fecal Material
Published on: September 29, 2017
UV-light-induced conversion and aggregation of prion proteins
Lars Redecke1, Stephan Binder, Mohammed I Y Elmallah
1Institute of Biochemistry and Molecular Biology, Department of Chemistry, University of Hamburg, Germany.
Free Radical Biology & Medicine
|March 3, 2009
Summary
UVB radiation induces prion protein (PrP) aggregation via two pathways, leading to either precipitation or soluble beta-oligomers. This study identifies a photo-trigger for PrP refolding, aiding conversion process analysis.
Area of Science:
- Biochemistry
- Neuroscience
- Structural Biology
Background:
- Prion diseases are fatal neurodegenerative disorders.
- Oxidative stress plays a key role in prion disease pathology.
- Prion protein (PrP) structural conversion underlies disease pathogenesis.
Purpose of the Study:
- To investigate the structural consequences of UVB radiation on prion protein (PrP).
- To explore the pathways of PrP aggregation induced by photo-oxidation.
- To identify potential photo-triggers for PrP refolding.
Main Methods:
- Recombinant murine and human prion proteins were exposed to UVB radiation.
- Circular dichroism and dynamic light scattering were used to analyze structural changes.
- PrP aggregation pathways and oligomer formation were characterized.
Main Results:
- UVB radiation induced PrP aggregation through two distinct pathways: precipitation or formation of soluble beta-oligomers.
- Pathway selection depended on PrP chromophoric properties and oxidation susceptibility.
- Oligomers formed share similarities with those induced by other destabilizing triggers.
- A novel photo-trigger capable of inducing PrP refolding was identified.
Conclusions:
- Partly unfolded PrP intermediates are likely precursor molecules in aggregation.
- UVB radiation provides a novel tool to study PrP structural conversion.
- The identified photo-trigger has biotechnological implications for analyzing PrP conversion dynamics.
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