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Thioflavins are that are available as at least two compounds, namely Thioflavin T and Thioflavin S. Both are used for histology staining and biophysics studies of protein aggregation. In particular, these dyes have been used since 1959 to investigate amyloid formation. They are also used in biophysical studies of the electrophysiology of bacteria. Thioflavins are corrosive, Irritation, and acutely toxic, causing serious eye damage. Thioflavin T has been used in research into Alzheimer's disease and other neurodegenerative diseases.
When it binds to beta sheet-rich structures, such as those in amyloid aggregates, the dye displays enhanced fluorescence and a characteristic red shift of its emission spectrum.H. LeVine III, Methods in Enzymology. 309, 274 (1999) Additional studies also consider fluorescence changes as result of the interaction with double stranded DNA. This change in fluorescent behavior can be caused by many factors that affect the excited state electron density of thioflavin T, including binding to a rigid, highly-ordered nanopocket, and specific chemical interactions between thioflavin T and the nanopocket.
Prior to binding to an amyloid fibril, thioflavin T emits weakly around 427 nm. Quenching effects of the nearby excitation peak at 450 nm is suspected to play a role in minimizing emissions.
When excited at 450 nm, thioflavin T produces a strong fluorescence signal at approximately 482 nm upon binding to amyloids. Thioflavin T molecule consists of a phenylamine and a benzothiazole ring connected through a carbon-carbon bond. These two rings can rotate freely when the molecule is in solution. The free rotation of these rings results in quenching of any excited state generated by photon excitation. However, when thioflavin T binds to amyloid fibrils, the two rotational planes of the two rings become immobilized and therefore, this molecule can maintain its excited state.
Thioflavin T fluorescence is often used as a diagnostic of amyloid structure, but it is not perfectly specific for amyloid. Depending on the particular protein and experimental conditions, thioflavin T may or may not undergo a spectroscopic change upon binding to precursor monomers, small oligomers, unaggregated material with a high beta sheet content, or even alpha helix-rich proteins. Conversely, some amyloid fibers do not affect thioflavin T fluorescence, raising the prospect of false negative results.
In adult C. elegans, exposure to thioflavin T results "in a profoundly extended lifespan and slowed aging" at some levels, but decreased lifespan at higher levels.
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