The lichen derived compound, otherwise known as Citrus Red 2 and E121, has been used for centuries to colour fabrics and food. Now research has suggested the compound may reduce the abundance small amyloid protein aggregates that are considered to be toxic and cause neuronal dysfunction and memory impairment in Alzheimer's disease.
Writing in Nature Chemical Biology, researchers from the Max Delbrueck Center for Molecular Medicine, in Germany, found that the food dye – and a related molecule known as O4 – bind preferentially to small the amyloid aggregates and promote their conversion into larger, mature plaques, which researchers assume to be largely non-toxic.
"This is a new mechanism," said Professor Erich Wanker, one of the researchers involved in the study.
"Up to now it has been considered to be very difficult to stop the formation of small toxic protein assemblies. If our hypothesis is correct that the small aggregates, which are precursors of plaques, indeed cause neuronal death, with O4 we would have a new mechanism to attack the disease," he explained.
The mis-folding of protein is considered to be the cause of many degenerative diseases that affect the nervous system, including Alzheimer's, Parkinson's and Huntington's disease.
The research team explained that such diseases develop in a multistep process whereby proteins misfold and accumulate into large plaques.
It is assumed, they noted, that small mis-folded protein aggregates – that are the precursors to larger mature plaques – are toxic to nerve cells, thus leading to the destruction of nerve cells and a decline in cognitive and/or central nervous functioning.
Wanker and his colleagues had previously discovered that EGCG (Epigallocatechin-3-gallate), a natural chemical compound found in green tea, rendered the small toxic amyloid assemblies found in Alzheimer’s and
With orcein and O4 the team believe they have now discovered a new mechanism to eliminate these small protein aggregates.
They noted that instead of remodeling protein plaques – as occurs with EGCG – the dyes reduce the abundance of amyloid aggregates by accelerating the formation of large plaques.
However, Wanker and his team explained that it remains to be seen whether O4 can also be effective against small amounts of misfolded proteins in the brains of Alzheimer's patients, and whether the accelerated formation of larger plaques can indeed reduce the signs and symptoms of Alzheimer's disease in humans.
They said that further studies are required to address whether the accelerated formation of large plaques can be a therapeutic approach.
"We hope that our findings will stimulate research activities in this direction," said Wanker.
Source: Nature Chemical Biology
Published online ahead of print, doi:10.1038/nchembio.719
“Small-molecule conversion of toxic oligomers to nontoxic β-sheet–rich amyloid fibrils”
Authors: J. Bieschke, M. Herbst, T. Wiglenda, R.P. Friedrich, A. Boeddrich, et a