Search results for "Amyloid"
showing 10 items of 494 documents
In vitro fibrillogenesis of the amyloid beta 1-42 peptide: cholesterol potentiation and aspirin inhibition.
2002
Understanding the formation of extracellular amyloid neurofibrillar bundles/senile plaques and their role in the development of Alzheimer's disease is of considerable interest to neuroscientists and clinicians. Major components of the extracellular neurofibrillar bundles are polymerized amyloid beta (Abeta) peptides (1-40), (1-42) and (1-43), derived in vivo from the soluble amyloid precursor protein (sAPP) by proteolytic (beta- and gamma-secretase) cleavage. The Abeta(1-42) peptide is widely considered to be of greatest significance in relation to the pathogenesis of Alzheimer's disease. A well-defined ultrastructural characteristic within Alzheimer dense plaques is the presence of helical…
Cholesterol binding to amyloid-β fibrils: A TEM study
2008
There is increasing interest in the role of brain cholesterol in Alzheimer's disease and the contribution of cholesterol to the formation of amyloid plaques. This paper presents a TEM study showing the binding of soluble approximately 10 nm diameter cholesterol-PEG 600 micelles to amyloid-beta(1-42) (Abeta(1-42)) fibrils formed either in the presence of this cholesterol derivative or to preformed fibrils generated under four different fibrillogenesis conditions. Specimens negatively stained with uranyl acetate revealed that during 24 h fibrillogenesis at 37 degrees C the cholesterol-PEG micelles bound periodically to Abeta(1-42) protofibrils and apparently also formed a thin smooth unbroken…
Detection of Amyloid-β Fibrils Using Track-Etched Nanopores: Effect of Geometry and Crowding
2021
Several neurodegenerative diseases have been linked to proteins or peptides that are prone to aggregate in different brain regions. Aggregation of amyloid-β (Aβ) peptides is recognized as the main cause of Alzheimer's disease (AD) progression, leading to the formation of toxic Aβ oligomers and amyloid fibrils. The molecular mechanism of Aβ aggregation is complex and still not fully understood. Nanopore technology provides a new way to obtain kinetic and morphological aspects of Aβ aggregation at a single-molecule scale without labeling by detecting the electrochemical signal of the peptides when they pass through the hole. Here, we investigate the influence of nanoscale geometry (conical an…
N-Terminal amino acid sequence analysis indicates that isolated atrial amyloid is derived from atrial natriuretic peptide
1988
Isolated atrial amyloid, the most frequent senile cardiac amyloid type, was chemically analysed. Amyloid fibrils obtained from a patient (NIP) were extracted and the predominant low-molecular-weight polypeptide (approximately 3.5 kDa, designated ASc2 NIP) was isolated by size exclusion high performance liquid chromatography in 60% formic acid. N-Terminal amino acid sequence analysis of this polypeptide was identical to that of the atrial natriuretic peptide alpha-hANP for the first 12 residues determined.
Kinetics of different processes in human insulin amyloid formation.
2007
Human insulin has long been known to form amyloid fibrils under given conditions. The molecular basis of insulin aggregation is relevant for modeling the amyloidogenesis process, which is involved in many pathologies, as well as for improving delivery systems, used for diabetes treatments. Insulin aggregation displays a wide variety of morphologies, from small oligomeric filaments to huge floccules, and therefore different specific processes are likely to be intertwined in the overall aggregation. In the present work, we studied the aggregation kinetics of human insulin at low pH and different temperatures and concentrations. The structure and the morphogenesis of aggregates on a wide range…
(E)-2-Cyano-3-(5′-piperidin-1-yl-2,2′-bithien-5-yl)acrylic Acid: A Fluorescent Probe for Detecting Prefibrillar Oligomers
2013
The synthesis of (E)-2-cyano-3-(5′-piperidin-1-yl-2,2′-bithien-5-yl)acrylic acid, a novel amyloid aggregation fluorescent probe, is reported. This new probe is able to monitor soluble oligomeric aggregates after 24 h, at which time Thioflavin T emission, commonly used to monitor amyloid fibril formation, remains unchanged. Atomic force microscopy, native polyacrylamide gel electrophoresis, and dynamic light scattering confirm that the earlier stages of aggregation are prefibrillar oligomeric species not possessing the amyloid structure. This new molecular scaffold expands the toolbox of fluorescent probes for the identification of prefibrillar oligomers, which is needed in studies aimed at …
Concanavalin A aggregation and toxicity on cell cultures
2009
A number of neurodegenerative diseases are known to involve protein aggregation. Common mechanisms and structural properties of amyloids are thought to be involved in aggregation-related cytotoxicity. In this context we propose an experimental study on Concanavalin A (Con A) aggregation and use it as a model to study the relationship between cell toxicity and aggregation processes. Depending on solution conditions, Con A aggregation has been monitored by static and dynamic light scattering, Thioflavin T emission, and FTIR absorption. The morphology of different aggregate species was verified by means of Atomic Force Microscopy and Confocal Microscopy. During the aggregation pathway the nati…
Design and synthesis of new trehalose-conjugated pentapeptides as inhibitors of Aβ(1-42) fibrillogenesis and toxicity
2009
Aggregation of the amyloid A? peptide and its accumulation into insoluble deposits (plaques) are believed to be the main cause of neuronal dysfunction associated with Alzheimer's disease (AD); small molecules that can interfere with the A? amyloid fibril formation are therefore of interest for a potential therapeutic strategy. Three new trehalose-conjugated peptides of the well known ?-sheet breaker peptide iA?5p,were synthesized. The disaccharide was covalently attached to different sites of the LPFFD peptide chain, i.e. at the N-terminus, C-terminus or at the Asp side chain. CD spectroscopy in different solvents was used to assess changes in the peptide conformation of these compounds. Th…
Thermodynamic versus Conformational Metastability in Fibril-Forming Lysozyme Solutions
2012
The role of intermolecular interaction in fibril-forming protein solutions and its relation with molecular conformation is a crucial aspect for the control and inhibition of amyloid structures. Here, we study the fibril formation and the protein-protein interactions of lysozyme at acidic pH and low ionic strength. The amyloid formation occurs after a long lag time and is preceded by the formation of oligomers, which seems to be off-pathway with respect to fibrillation. By measuring the osmotic isothermal compressibility and the collective diffusion coefficient of lysozyme in solution, we observe that the monomeric solution is kept in a thermodynamically metastable state by strong electrosta…