Search results for "FIBRILLOGENESIS"
showing 10 items of 28 documents
Entrapment of A Beta 1-40 peptide in unstructured aggregates
2012
Recognizing the complexity of the fibrillogenesis process provides a solid ground for the development of therapeutic strategies aimed at preventing or inhibiting protein-protein aggregation. Under this perspective, it is meaningful to identify the possible aggregation pathways and their relative products. We found that Aβ-peptide dissolved in a pH 7.4 solution at small peptide concentration and low ionic strength forms globular aggregates without typical amyloid β-conformation. ThT binding kinetics was used to monitor aggregate formation. Circular dichroism spectroscopy, AFM imaging, static and dynamic light scattering were used for structural and morphological characterization of the aggre…
Carnosine Inhibits Aβ42Aggregation by Perturbing the H-Bond Network in and around the Central Hydrophobic Cluster
2013
Aggregation of the amyloid-β peptide (Aβ) into fibrillar structures is a hallmark of Alzheimer's disease. Thus, preventing self-assembly of the Aβ peptide is an attractive therapeutic strategy. Here, we used experimental techniques and atomistic simulations to investigate the influence of carnosine, a dipeptide naturally occurring in the brain, on Aβ aggregation. Scanning force microscopy, circular dichroism and thioflavin T fluorescence experiments showed that carnosine does not modify the conformational features of Aβ42 but nonetheless inhibits amyloid growth. Molecular dynamics (MD) simulations indicated that carnosine interacts transiently with monomeric Aβ42 by salt bridges with charge…
Valorization of apple peels through the study of the effects on the amyloid aggregation process of ?-casein
2021
Waste valorization represents one of the main social challenges when promoting a circular economy and environmental sustainability. Here, we evaluated the effect of the polyphenols extracted from apple peels, normally disposed of as waste, on the amyloid aggregation process of ?-casein from bovine milk, a well-used amyloidogenic model system. The effect of the apple peel extract on protein aggregation was examined using a thioflavin T fluorescence assay, Congo red binding assay, circular dichroism, light scattering, and atomic force microscopy. We found that the phenolic extract from the peel of apples of the cultivar "Fuji", cultivated in Sicily (Caltavuturo, Italy), inhibited ?-casein fib…
Copper(ii) and zinc(ii) dependent effects on Aβ42 aggregation: a CD, Th-T and SFM study
2013
A? aggregation is a central event in Alzheimer's disease (AD). In vitro evidence indicates that A? aggregation and fibrillogenesis are significantly influenced by the employed experimental conditions. Indeed, although it is widely established that metal ions, such as copper and zinc, have significant effects on the A? aggregation process, their actual role in A? fibrillogenesis is still debated. In this work the effects of a molar excess of zinc(ii) and/or copper(ii) ions on the A?42 aggregation process and the morphology of the resultant aggregates have been compared in samples exhibiting different initial conformations. CD spectroscopy, Th-T-induced fluorescence and Scanning Force Microsc…
Introduction and Technical Survey: Protein Aggregation and Fibrillogenesis
2012
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…
Influence of saline and pH on collagen type I fibrillogenesis in vitro: Fibril polymorphism and colloidal gold labelling
2007
We have produced different collagen type I fibrils by in vitro fibrillogenesis of acetic acid-soluble collagen within the pH range 2.5-9.0, in the presence and absence of 150 mM NaCl. The varying relatively stable molecular assemblies and polymorphic fibrillar end-products produced after 24 h incubation have been assessed and compared by the TEM study of specimens negatively stained with uranyl acetate. In the presence of 150 mM NaCl, the assembly of collagen at low pH (2.5) leads to the formation of initial molecular aggregates that progressively link together at slightly higher pH (5.0) to form sub-fibrils and spindle-shaped D-banded bundles of sub-fibrils. At pH 6.0 these D-banded bundle…
An Aqueous Extract ofWithania somniferaRoot Inhibits Amyloid β Fibril FormationIn Vitro
2011
The ability of an aqueous extract of W. somnifera L. Dunal (Family: Solanaceae) roots to inhibit fibril formation by the amyloid-β peptide in vitro was investigated. W. somnifera is used extensively in traditional Ayurvedic medicine as a nerve tonic with reputed memory enhancing properties. Inhibition of fibrillogenesis measured by transmission electron microscopy and ThT fluorescence assay showed that an aqueous extract of W. somnifera strongly inhibited Aβ fibril formation in a concentration-dependent manner, when compared with control samples. These results suggest that the aqueous extract of W. somnifera root has an ability to inhibit the formation of mature amyloid-β fibrils in vitro, …
Casein-loaded proteoliposomes: novel delivery strategy to inhibit Aβ1-40 fibrillogenesis in Alzheimer disease
2018
Background: Alzheimer's disease (AD) is a chronic and progressive syndrome, which represents the most common cause of dementia worldwide. A pathological and characteristic AD hallmark is the deposition of amyloid plaques, composed by well-ordered amyloid β-peptide (Aβ) fibers, in brain tissue. The Aβ aggregation process follows typical nucleation-polymerization kinetics, characterized by structural intermediates with specific dimensions, morphologies and cytotoxic activity. Some evidences shifted researchers’ attention to smaller soluble Aβ prefibrillar oligomers as they result the most toxic species. Therefore, novel therapeutic strategies target oligomers or prefibrillar aggregates rather…
Casein-loaded proteoliposomes: Drug Delivery Systems and Potential Inhibitors in Aβ1-40 Fibrillogenesis
2018
Alzheimer's disease (AD) represents the most common cause of dementia worldwide. The early symptom is usually a short-term memory loss, followed by symptoms including problems with language, disorientation, mood swings, loss of motivation, not managing self-care, and behavioral issues, until loss of body functions and, ultimately, death. The cause of AD is poorly understood and the diagnosis is complex. One of the main AD hallmarks is the extracellular deposition in brain tissue of proteinaceous amyloid plaques, composed by well-ordered fibrillary aggregates of the amyloid β-peptide (Aβ). The Aβ aggregation process follows typical nucleation-polymerization kinetics, characterized by structu…
DECORIN EFFECTS ON PROTEOMIC PROFILING OF BREAST CANCER CELLS: AN UPDATED STUDY
2015
The malignant carcinomas are characterized by several capabilities acquired by the neoplastic cells, among which the ability to invade the extracellular matrix (ECM) and to establish a crosstalk with several ECM components. Under this respect, the extracellular microenvironment is an entity extraordinarily rich of information with opposite signals. Our group has long undertaken the study of the effects of ECM molecules on the behavior of cancer cells in vitro. Among the studied molecules, the decorin was found to exert a non-permissive effect on the growth and motility of the transfected tumor cells. The decorin, belongs to the family of small leucine-rich proteoglycans (SLRP) and is involv…