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Full-Text Articles in Social and Behavioral Sciences
The Two-Faced Nature Of Small Heat Shock Proteins: Amyloid Assembly And The Inhibition Of Fibril Formation. Relevance To Disease States, Heath W. Ecroyd, S Meehan, John A. Carver
The Two-Faced Nature Of Small Heat Shock Proteins: Amyloid Assembly And The Inhibition Of Fibril Formation. Relevance To Disease States, Heath W. Ecroyd, S Meehan, John A. Carver
Faculty of Science - Papers (Archive)
The ability of small heat-shock proteins (sHsps) such as alphaB-crystallin to inhibit the amorphous (disordered) aggregation of varied target proteins in a chaperone-like manner has been well described. The mechanistic details of this action are not understood. Amyloid fibril formation is an alternative off-folding pathway that leads to highly ordered beta-sheet-containing aggregates. Amyloid fibril formation is associated with a broad range of protein conformational diseases such as Alzhiemer's, Parkinson's and Huntington's and sHsp expression is elevated in the protein deposits that are characteristic of these disease states. The ability of sHsps to prevent fibril formation has been less well characterised. …
Carboxymethylated-K-Casein: A Convenient Tool For The Identification Of Polyphenolic Inhibitors Of Amyloid Fibril Formation, John A. Carver, Peter J. Duggan, Heath Ecroyd, Yanqin Liu, Adam G. Meyer, C E. Tranberg
Carboxymethylated-K-Casein: A Convenient Tool For The Identification Of Polyphenolic Inhibitors Of Amyloid Fibril Formation, John A. Carver, Peter J. Duggan, Heath Ecroyd, Yanqin Liu, Adam G. Meyer, C E. Tranberg
Faculty of Science - Papers (Archive)
Reduced and carboxymethylated-κ-casein (RCM-κ-CN) is a milk-derived amyloidogenic protein that readily undergoes nucleation-dependent aggregation and amyloid fibril formation via a similar pathway to disease-specific amyloidogenic peptides like amyloid beta (Aβ), which is associated with Alzheimer’s disease. In this study, a series of flavonoids, many known to be inhibitors of Aβ fibril formation, were screened for their ability to inhibit RCM-κ-CN fibrilisation, and the results were compared with literature data on Aβ inhibition. Flavonoids that had a high degree of hydroxylation and molecular planarity gave good inhibition of RCM-κ-CN fibril formation. IC50 values were between 10- and 200-fold higher with RCM-κ-CN …
Alphab-Crystallin Inhibits The Cell Toxicity Associated With Amyloid Fibril Formation By Kappa-Casein And The Amyloid-Beta Peptide, Francis C. Dehle, Heath Ecroyd, Ian F. Musgrave, John A. Carver
Alphab-Crystallin Inhibits The Cell Toxicity Associated With Amyloid Fibril Formation By Kappa-Casein And The Amyloid-Beta Peptide, Francis C. Dehle, Heath Ecroyd, Ian F. Musgrave, John A. Carver
Faculty of Science - Papers (Archive)
Amyloid fibril formation is associated with diseases such as Alzheimer’s, Parkinson’s, and prion diseases. Inhibition of amyloid fibril formation by molecular chaperone proteins, such as the small heat-shock protein αB-crystallin, may play a protective role in preventing the toxicity associated with this form of protein misfolding. Reduced and carboxymethylated κ-casein (RCMκ-CN), a protein derived from milk, readily and reproducibly forms fibrils at physiological temperature and pH. We investigated the toxicity of fibril formation by RCMκ-CN using neuronal model PC12 cells and determined whether the inhibition of fibril formation altered its cell toxicity. To resolve ambiguities in the literature, we also …
Protein Chemistry Of Amyloid Fibrils And Chaperones: Implications For Amyloid Formation And Disease, Justin J. Yerbury, Janet R. Kumita
Protein Chemistry Of Amyloid Fibrils And Chaperones: Implications For Amyloid Formation And Disease, Justin J. Yerbury, Janet R. Kumita
Faculty of Science - Papers (Archive)
Understanding the mechanisms by which amyloid fibrils are formed, both in vivo and in vitro, is vital for developing methods to treat and prevent debilitating deposition diseases such as Alzheimer's disease, Parkinson's disease, type II diabetes and systemic amyloidoses. In recent years, computer modelling and biophysical studies have broadened our understanding of the biochemical mechanisms underpinning protein aggregation. As a result, it is now believed that the ability to form fibrils is an intrinsic property of polypeptide chains and not isolated to disease-related proteins or peptides. Molecular chaperones are a diverse group of functionally related proteins well known for their …
The Dissociated Form Of Kappa-Casein Is The Precursor To Its Amyloid Fibril Formation, Heath Ecroyd, David Thorn, Yanqin Liu, John Carver
The Dissociated Form Of Kappa-Casein Is The Precursor To Its Amyloid Fibril Formation, Heath Ecroyd, David Thorn, Yanqin Liu, John Carver
Faculty of Science - Papers (Archive)
Bovine milk kappa-casein forms a self-associating oligomeric micelle-like species, in equilibrium with dissociated forms. In its native form, intra- and inter-molecular disulfide bonds lead to the formation of multimeric species ranging from monomers to decamers. When incubated under conditions of physiological pH and temperature, both reduced and non-reduced kappa-casein form highly structured beta-sheet amyloid fibrils. We investigated whether the precursor to kappa-casein fibril formation is a dissociated state of the protein or its oligomeric micelle-like form. We show that reduced kappa-casein is capable of forming fibrils well below its critical micelle concentration, i.e. at concentrations where only dissociated forms of …