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Protein misfolding, functional amyloid, and human disease.
The relative importance of the common main-chain and side-chain interactions in determining the propensities of proteins to aggregate is discussed and some of the evidence that the oligomeric fibril precursors are the primary origins of pathological behavior is described.
Protein folding and misfolding
The manner in which a newly synthesized chain of amino acids transforms itself into a perfectly folded protein depends both on the intrinsic properties of the amino-acid sequence and on multiple
Hydrodynamic radii of native and denatured proteins measured by pulse field gradient NMR techniques.
Evidence is found for significant coupling between local and global features of the conformational ensembles adopted in such states and the effective dimensions of the polypeptide chain are found to depend significantly on the level of persistence of regions of secondary structure or features within a conformational ensemble.
Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases
This finding provides added evidence that avoidance of protein aggregation is crucial for the preservation of biological function and suggests common features in the origins of this family of protein deposition diseases.
Rationalization of the effects of mutations on peptide andprotein aggregation rates
It is shown that the intrinsic effects of specific mutations on the rates of aggregation of unfolded polypeptide chains can be correlated to a remarkable extent with changes in simple physicochemical properties such as hydrophobicity, secondary structure propensity and charge.
The amyloid state and its association with protein misfolding diseases
The spacing between polypeptide chains along the fibril axis is constant to a good approximation even for very different polypeptic sequences, a generic property arising from the common inter-side chain hydrogen bonding constraints.
Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution
The 'new view' of these diseases suggests that other degenerative conditions could have similar underlying origins to those of the amyloidoses, and suggests some intriguing new factors that could be of great significance in the evolution of biological molecules and the mechanisms that regulate their behaviour.
Protein Misfolding, Amyloid Formation, and Human Disease: A Summary of Progress Over the Last Decade.
This review describes this field of science with particular reference to the advances that have been made over the last decade in understanding of its fundamental nature and consequences and shows evidence that a complex proteostasis network actively combats protein aggregation.
Protein misfolding, evolution and disease.
  • C. Dobson
  • Medicine
    Trends in biochemical sciences
  • 1 September 1999
Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism
These results reveal that the aggregation of A β42 is promoted by a positive feedback loop that originates from the interactions between the monomeric and fibrillar forms of this peptide, and suggest that perturbation of the secondary nucleation pathway identified in this study could be an effective strategy to control the proliferation of neurotoxic Aβ42 oligomers.