High Pressure Induces Scrapie-like Prion Protein Misfolding and Amyloid Fibril Formation†

Biochemistry ◽  
2004 ◽  
Vol 43 (22) ◽  
pp. 7162-7170 ◽  
Author(s):  
Joan Torrent ◽  
Maria Teresa Alvarez-Martinez ◽  
Marie-Cécile Harricane ◽  
Frédéric Heitz ◽  
Jean-Pierre Liautard ◽  
...  
Keyword(s):  
High Pressure ◽  
Prion Protein ◽  
Protein Misfolding ◽  
Amyloid Fibril ◽  
Fibril Formation ◽  
Amyloid Fibril Formation

Structural mechanisms of oligomer and amyloid fibril formation by the prion protein

2018 ◽  
Vol 54 (49) ◽  
pp. 6230-6242 ◽  
Author(s):  
Ishita Sengupta ◽  
Jayant B. Udgaonkar
Keyword(s):  
Prion Protein ◽  
Amyloid Fibril ◽  
Fibril Formation ◽  
Aggregation Mechanism ◽  
Amyloid Fibril Formation ◽  
Structural Mechanisms

The aggregation mechanism of the prion protein is highly heterogeneous.

Aggregation and Amyloid Fibril Formation of the Prion Protein Is Accelerated in the Presence of Glycogen

2008 ◽  
Vol 11 (2) ◽  
pp. 365-369 ◽  
Author(s):  
Giannantonio Panza ◽  
Jan Stöhr ◽  
Eva Birkmann ◽  
Detlev Riesner ◽  
Dieter Willbold ◽  
...  
Keyword(s):  
Prion Protein ◽  
Amyloid Fibril ◽  
Fibril Formation ◽  
Amyloid Fibril Formation

scholarly journals Higher susceptibility to amyloid fibril formation of the recombinant ovine prion protein modified by transglutaminase

2012 ◽  
Vol 1822 (10) ◽  
pp. 1509-1515 ◽  
Author(s):  
Angela Sorrentino ◽  
Concetta Valeria L. Giosafatto ◽  
Ivana Sirangelo ◽  
Carmela De Simone ◽  
Prospero Di Pierro ◽  
...  
Keyword(s):  
Prion Protein ◽  
Amyloid Fibril ◽  
Fibril Formation ◽  
Amyloid Fibril Formation

scholarly journals Dynamics of oligomer populations formed during the aggregation of Alzheimer’s Aβ42 peptide

2020 ◽  
Author(s):  
Thomas C. T. Michaels ◽  
Andela Šarić ◽  
Samo Curk ◽  
Katja Bernfur ◽  
Paolo Arosio ◽  
...  
Keyword(s):  
Protein Misfolding ◽  
Amyloid Fibrils ◽  
Amyloid Fibril ◽  
Fibril Formation ◽  
Therapeutic Interventions ◽  
Molecular Pathways ◽  
Amyloid Fibril Formation ◽  
Aβ42 Peptide ◽  
Heterogeneous Ensemble ◽  
Misfolding Diseases

AbstractOligomeric aggregates populated during the aggregation of the Aβ42 peptide have been identified as potent cytotoxins linked to Alzheimer’s disease, but the fundamental molecular pathways that control their dynamics have yet to be elucidated. By developing a general approach combining theory, experiment, and simulation, we reveal in molecular detail the mechanisms of Aβ42 oligomer dynamics during amyloid fibril formation. Even though all mature amyloid fibrils must originate as oligomers, we find that most Aβ42 oligomers dissociate to their monomeric precursors without forming new fibrils. Only a minority of oligomers converts into fibrillar species. Moreover, the heterogeneous ensemble of oligomeric species interconverts on timescales comparable to aggregation. Our results identify fundamentally new steps that could be targeted by therapeutic interventions designed to combat protein misfolding diseases.

scholarly journals Thermodynamic and kinetic design principles for amyloid-aggregation inhibitors

2020 ◽  
Vol 117 (39) ◽  
pp. 24251-24257 ◽  
Author(s):  
Thomas C. T. Michaels ◽  
Andela Šarić ◽  
Georg Meisl ◽  
Gabriella T. Heller ◽  
Samo Curk ◽  
...  
Keyword(s):  
Protein Misfolding ◽  
Amyloid Fibril ◽  
Complex Problem ◽  
Fibril Formation ◽  
Amyloid Aggregation ◽  
Design And Optimization ◽  
Amyloid Fibril Formation ◽  
Potent Inhibition ◽  
General Physical ◽  
Misfolding Diseases

Understanding the mechanism of action of compounds capable of inhibiting amyloid-fibril formation is critical to the development of potential therapeutics against protein-misfolding diseases. A fundamental challenge for progress is the range of possible target species and the disparate timescales involved, since the aggregating proteins are simultaneously the reactants, products, intermediates, and catalysts of the reaction. It is a complex problem, therefore, to choose the states of the aggregating proteins that should be bound by the compounds to achieve the most potent inhibition. We present here a comprehensive kinetic theory of amyloid-aggregation inhibition that reveals the fundamental thermodynamic and kinetic signatures characterizing effective inhibitors by identifying quantitative relationships between the aggregation and binding rate constants. These results provide general physical laws to guide the design and optimization of inhibitors of amyloid-fibril formation, revealing in particular the important role of on-rates in the binding of the inhibitors.

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