ThT influences Abeta(1-40) aggregation process

Thioflavin T templates amyloid β(1–40) conformation and aggregation pathway

Aβ(1-40) peptide supramolecular assembly and fibril formation processes are widely recognized to have direct implications in the progression of Alzheimer's disease. The molecular basis of this biological process is still unknown and there is a strong need of developing effective strategies to control the occurring events. To this purpose the exploitation of small molecules interacting with Aβ aggregation represents one of the possible routes. Moreover, the use specific labeling has represented so far one of the most common and effective methods to investigate such a process. This possibility in turn rests on the reliability of the probe/labels involved. Here we present evidences of the effe…

Thioflavin T Promotes Aβ(1−40) Amyloid Fibrils Formation

Fibrillogenesis of the small peptide Aβ(1-40) is considered to be the hallmark of Alzheimer's disease. Some evidence indicates small oligomers, rather than mature fibrils, as the key cytotoxic agents. The fluorescent dye Thioflavin T (ThT) is often used to detect amyloid deposits in both in vivo and in vitro experiments, and it is used to study kinetic measurements, under the fundamental hypothesis that this probe does not influence the aggregation processes. We report experimental data showing that ThT may promote the Aβ(1-40) peptide amyloid aggregation changing solvent-peptide interactions and stabilizing more ordered β-like conformation. This finding has a two-fold importance: It is a f…

Aggregation processes of intrinsically disordered proteins: influence of the environment

Modulation of α-Synuclein Aggregation Process and Fibril Stability by Co-solvents

Amyloid fibrils are involved in several amyloid-related pathologies such as Parkinson's disease, Alzheimer's disease and type II diabetes. As a result, scientific community is nowadays addressing considerable efforts towards the comprehension of fibrillation mechanisms, particularly focusing on how they are affected by environmental conditions, small molecules and/or membrane presence. In this scenario, alpha-synuclein (aSN), a small protein involved in Parkinson's disease, represents a challenging model system for studying aggregation phenomena, and understanding the pathogenesis at molecular level. Indeed, it is poorly understood how fibril formation is linked to the progressive neurodege…

Thioflavin T triggers β amyloid peptide (1-40) fibrils formation.

Introduction A general characteristic of aggregation is the multiple interaction and cross-feedback among distinct mechanisms occurring at different hierarchical levels. The comprehension of the different species interconversion during aggregation is very important since emerging evidences indicate intermediate oligomeric aggregates as primary toxic species. In this context, Aβ amyloid peptide provides a challenging model for studying aggregation phenomena both for the complexity of its association process and for the direct implications in Alzheimer’s Disease. Aggregates growth conditions strongly affect the final morphology, the fibrillar molecular structure as well as the aggregation pat…

Interconnected mechanism in Abeta(1-40) peptide fibril formation

Trifluoroethanol modulates α-synuclein amyloid-like aggregate formation, stability and dissolution

The conversion of proteins into amyloid fibrils and other amyloid-like aggregates is closely connected to the onset of a series of age-related pathologies. Upon changes in environmental conditions, amyloid-like aggregates may also undergo disassembly into oligomeric aggregates, the latter being recognized as key effectors in toxicity. This indicates new possible routes for in vivo accumulation of toxic species. In the light of the recognized implication of α-Synuclein (αSN) in Parkinson's disease, we present an experimental study on supramolecular assembly of αSN with a focus on stability and disassembly paths of such supramolecular aggregate species. Using spectroscopic techniques, two-pho…