Amyloid

Molecular Details of the Apolipoprotein E and the Amyloid Beta Peptide Interaction: Analysis of a Potential Binding Site Responsible for ApoE4 Misfolding

by sebastian wärmländer

pH-dependence of the specific binding of Cu(II) and Zn(II) ions to the amyloid-beta peptide

by sebastian wärmländer

N‐terminal engineering of amyloid‐β‐binding Affibody molecules yields improved chemical synthesis and higher binding affinity

by sebastian wärmländer

Interaction of synthetic Alzheimer β -protein-derived analogs with aqueous aluminum: A low-field 27 Al NMR investigation

by Sandip Vyas

Stabilization of Secondary Structure of Alzheimer β-Protein by Aluminum(III) Ions and D-Asp Substitutions

by Sandip Vyas

Giant amyloid spherulites reveal their true colours

by Mike Smith

The prevalence of degenerative conditions such as Alzheimer's and Parkinson's disease amongst an increasingly elderly... more The prevalence of degenerative conditions such as Alzheimer's and Parkinson's disease amongst an increasingly elderly population has led to substantial research efforts into understanding the properties and structures of amyloid protein aggregates. One such aggregate, the amyloid spherulite, consists of a central core surrounded by long fibres of aggregated protein (fibrils) which grow radially outwards. Spherulites (5–50 μm in diameter) exhibit four white lobes when observed using crossed polarised microscopy, due to their birefringence. Here we report the growth of giant amyloid spherulites (GAS, diameters 0.4–1 mm) that produce colourful patterns when placed between crossed polarisers. A ray tracing model was developed that accounts for these patterns by calculating the effects of birefringence on light passing through the GAS. This new model links for the first time the optical properties of spherulites to the density and orientation of the fibrils, providing a route to understanding the formation of these important protein aggregates.

DHA diet reduces AD pathology in young APPswe/PS1ΔE9 transgenic mice: possible gender effects

by Yuan-Shih Jennifer Hu

Crystals of the hydrogenase maturation factor HypF N-terminal domain grown in microgravity, display improved internal order

by Camillo Rosano

2-Microglobulin H31Y Variant 3D Structure Highlights the Protein Natural Propensity Towards Intermolecular Aggregation

by Camillo Rosano

Time-Resolved Small-Angle X-Ray Scattering Study of the Early Formation of Amyloid Protofibrils on a Apomyoglobin Mutant

by Maria Grazia Ortore

Information-Selectivity of Beta-Amyloid Pathology in an Associative Memory Model

by Mark Rowan

Factors affecting the formation of insulin amyloid spherulites

by Mike Smith

Co-authored with V. Fodera, J.S. Sharp, C.J. Roberts, A.M. Donald

Thermally induced amyloid aggregation of bovine insulin can produce a number of distinct aggregate morphologies. In... more Thermally induced amyloid aggregation of bovine insulin can produce a number of distinct aggregate morphologies. In this work amyloid spherulites were analysed using cross polarized optical microscopy and light scattering. A new semi-quantitative methodology to estimate the balance of spherulites and free fibrils is reported and, from this analysis, the effects of pH, temperature, salt, and protein concentration on spherulite formation were quantitatively determined for the first time. The number and size of spherulites measured with polarized light microscopy were related to changes in the colloidal stability of the solution and fibril nucleation times (measured by static light scattering). Importantly, changes in pH between 1.75 and 2 were found to result in a dramatic decrease in the spherulite radii, which were related to differences in the conformational stability of the protein. Moreover, estimates of the final spherulite volume fraction clearly indicate that amyloid spherulite formation is the dominant pathway for insulin aggregation in HCl solutions at low pH and protein concentrations below ∼5 mg ml−1, with the balance shifting towards fibrils as the concentration increases.

Time-resolved small-angle x-ray scattering study of the early stage of amyloid formation of an apomyoglobin mutant

by Maria Grazia Ortore

An analytical solution to the kinetics of breakable filament assembly

by Eugene Terentjev

Nucleated polymerization with secondary pathways. I. Time evolution of the principal moments

by Eugene Terentjev

Morphology and Persistence Length of Amyloid Fibrils are Correlated to Peptide Molecular Structure

by Maarten Engel

Corianne C. vandenAkker , Maarten F.M. Engel , Krassimir P. Velikov , Mischa Bonn , and Gijsje H. Koenderink, J. Am. Chem. Soc., Just Accepted Manuscript DOI: 10.1021/ja206513r

The formation of amyloid fibrils is a self-assembly process of peptides or proteins. The superior mechanical... more The formation of amyloid fibrils is a self-assembly process of peptides or proteins. The superior mechanical properties of these fibrils make them interesting for materials science, but constitute a problem in amyloid-related diseases. Amyloid structures tend to be polymorphic and their structure depends on growth conditions. To understand and control the assembly process, insights into the relation between the mechanical properties and molecular structure are essential. We prepared long, straight as well as short, worm-like β-lactoglobulin amyloid fibrils and determined their morphology and persistence length by atomic force microscopy (AFM) and the molecular conformation using vibrational sum-frequency generation (VSFG) spectrosco-py. We show that long fibrils with near-100% β-sheet content have a 40-times higher persistence length than short, worm-like fibrils with β-sheet contents below 80%.

The Assembly of Individual Chaplin Peptides from Streptomyces coelicolor into Functional Amyloid Fibrils

by Beth Sawyer

The yeast prion protein Ure2: insights into the mechanism of amyloid formation

by Beth Sawyer

Ure2, a regulator of nitrogen metabolism, is the protein determinant of the [URE3] prion state in Saccharomyces... more Ure2, a regulator of nitrogen metabolism, is the protein determinant of the [URE3] prion state in Saccharomyces cerevisiae. Upon conversion into the prion form, Ure2 undergoes a heritable conformational change to an amyloid-like aggregated state and loses its regulatory function. A number of molecular chaperones have been found to affect the prion properties of Ure2. The studies carried out in our laboratory have been aimed at elucidating the structure of Ure2 fibrils, the mechanism of amyloid formation and the effect of chaperones on the fibril formation of Ure2.

Mechanism of Cis-Inhibition of PolyQ Fibrillation by PolyP: PPII Oligomers and the Hydrophobic Effect

by Josh Kurutz

Up‐regulation of P‐glycoprotein reduces intracellular accumulation of beta amyloid: investigation of P‐glycoprotein as a novel therapeutic target for Alzheimer's disease

by Alaa Abuznait