A5020069196- Prion Diseases and Protein Misfolding
- Alzheimer's disease research and treatments
- Advanced NMR Techniques and Applications
- Drug Transport and Resistance Mechanisms
- Neurological diseases and metabolism
Heinrich Heine University Düsseldorf
2018-2021
Forschungszentrum Jülich
2018-2021
Human PrP (huPrP) is a high-affinity receptor for oligomeric amyloid β (Aβ) protein aggregates. Binding of Aβ oligomers to membrane-anchored huPrP has been suggested trigger neurotoxic cell signaling in Alzheimer's disease, while an N-terminal soluble fragment can sequester and reduce their toxicity. Synthetic species are known be heterogeneous, dynamic, transient, rendering structural investigation particularly challenging. Here, using preserve by coprecipitating them into large...
Abstract The interaction of prion protein (PrP) and α-synuclein (αSyn) oligomers causes synaptic impairment that might trigger Parkinson’s disease other synucleinopathies. Here, we report αSyn (αSynO) cluster with human PrP (huPrP) into micron-sized condensates. Multivalency within is required for condensation, since clustering huPrP not observed monomeric αSyn. stoichiometry the heteroassemblies well defined an αSyn:huPrP molar ratio about 1:1. αSynO−huPrP high affinity, signified by slow...
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that affects millions of people worldwide. One AD hallmark the aggregation β-amyloid (Aβ) into soluble oligomers and insoluble fibrils. Several studies have reported rather than fibrils are most toxic species in progression. Aβ bind with high affinity to membrane-associated prion protein (PrP), leading signaling across cell membrane, which makes Aβ–PrP interaction an attractive therapeutic target. Here, probing this more...
ABSTRACT Human PrP (huPrP) is a high-affinity receptor for oligomeric Aβ. Synthetic Aβ species are known to be heterogeneous, dynamic and transient, rendering their structural investigation particularly challenging. Here, we used huPrP preserve oligomers by co-precipitating them into large hetero-assemblies investigate the conformation of Aβ(1-42) in complex solid-state MAS NMR spectroscopy. The disordered N-terminal region becomes immobilized therefore visible dipolar spectra without...