0000000000178393
AUTHOR
Nathaniel G.n. Milton
Polymorphism of Amyloid Fibrils and their Complexes with Catalase
Catalase binding to amyloid fibrils has been shown for the Alzheimer’s amyloid-β (Aβ), type 2 diabetes-associated islet amyloid polypeptide (IAPP) and Creutzfeldt-Jakob disease-associated prion protein (PrP). Catalase targets a specific domain with a GAII-like sequence and there are a number of other amyloid fibril-forming proteins that contain related sequences, such as the Parkinson’s associated α-synuclein protein and the Huntington disease protein Huntingtin. Using transmission electron microscopy (TEM) analysis, interactions show specific binding of catalase to some, but not all, fibrillar forms of Aβ, IAPP and PrP fragments, allowing determination of the fibrillar forms that contain a…
Cholesterol in Alzheimer’s Disease and other Amyloidogenic Disorders
The complex association of cholesterol metabolism and Alzheimer’s disease is presented in depth, including the possible benefits to be gained from cholesterol-lowering statin therapy. Then follows a survey of the role of neuronal membrane cholesterol in Aβ pore formation and Aβ fibrillogenesis, together with the link with membrane raft domains and gangliosides. The contribution of structural studies to Aβ fibrillogenesis, using TEM and AFM, is given some emphasis. The role of apolipoprotein E and its isoforms, in particular ApoE4, in cholesterol and Aβ binding is presented, in relation to genetic risk factors for Alzheimer’s disease. Increasing evidence suggests that cholesterol oxidation p…
Introduction and Technical Survey: Protein Aggregation and Fibrillogenesis
In this chapter we provided the overall background to the subject of protein aggregation and fibrillogenesis in amyloidogenesis, with introduction and brief discussion of the various topics that are included with the coming chapters. The division of the book into basic science and clinical science sections enables correlation of the topics to be made. The many proteins and peptides that have currently been found to undergo fibrillogenesis are tabulated. A broad technical survey is made, to indicate the vast array of techniques currently available to study aspects of protein oligomerization, aggregation and fibrillogenesis. These are split into three groups and tabulated, as the microscopica…
Polymorphism of amyloid-beta fibrils and its effects on human erythrocyte catalase binding.
The Alzheimer's amyloid-beta (Abeta) peptide exists as a number of naturally occurring forms due to differential proteolytic processing of its precursor molecule. Many of the Abeta peptides of different lengths form fibrils in vitro, which often show polymorphisms in the fibril structure. This study presents a TEM based analysis of fibril formation by eighteen different Abeta peptides ranging in length from 5 to 43 amino acids. Spectrophotometric analysis of Congo red binding to the fibrillar material has been assessed and the binding of human erythrocyte catalase (HEC) to Abeta fibrils has also been investigated by TEM. The results show that a diverse range of Abeta peptides form fibrils a…
In Vitro Techniques
Driven in part by the development of genomics, proteomics, and bioinformatics as new disciplines, there has been a tremendous resurgence of interest in physical methods to investigate macromolecular structure and function in the context of living cells. This volume in Methods in Cell Biology is devoted to biophysical techniques in vitro and their applications to cellular biology. The volume covers methods-oriented chapters on fundamental as well as cutting-edge techniques in molecular and cellular biophysics.This book is directed toward the broad audience of cell biologists, biophysicists, pharmacologists, and molecular biologists who employ classical and modern biophysical technologies or …
Fibril formation and toxicity of the non-amyloidogenic rat amylin peptide.
Full-length native rat amylin 1-37 has previously been widely shown to be unable to form fibrils and to lack the toxicity of the human amylin form leading to its use as a non-amyloidogenic control peptide. A recent study has suggested that rat amylin 1-37 forms amyloidogenic β-sheet structures in the presence of the human amylin form and suggested that this property could promote toxicity. Using TEM analysis we show here fibril formation by synthetic rat amylin 1-37 and 8-37 peptides when the lyophilized HPLC purified peptides are initially dissolved in 20 mM Tris-HCl. Dissolution of synthetic rat amylin 1-37 and 8-37 peptides in H(2)O or phosphate buffered saline failed to produce fibrils.…