New Delhi: One of the reasons behind dementia is a tiny protein that begins to malfunction and form abnormal shapes that interfere with neurons. Scientists have now found the hotspot where this deformation begins, pointing to a new target for dementia treatments.
The findings were published first in a research article in Proceedings of the National Academy of Sciences on 12 October, and the larger study by researchers at the University of California, Santa Barbara and Northwestern University, will follow soon on 16 October.
“We might have found a shortcut for the pharmacist or biochemist because instead of searching for everything, we can say, ‘Look for that hotspot. That’s the spot that matters’,” senior author Songi Han said in a statement.
The tau protein
At the centre of the findings is the tau protein, which usually supports the internal structure of nerve cells. In diseases such as Alzheimer’s, the tau protein misfolds and clumps into long fibres called fibrils that disrupt the functioning of neurons. One such misfolded tau protein can trigger another to turn into abnormal shapes too.
However, researchers have now found a spot on the tau protein’s surface that drives this process. Along the hydrophobic region water molecules form a cap-like structure. When two such matching hotspots meet, the water is released, allowing the tau proteins to bind.
“Once you know that aggregation-prone tau proteins always have a hotspot that is first attracted to the same site of tau that is stacked to fibrils, then you know there’s always some part of the protein that you can target to neutralize. If you know where to block its action of misfolding, you could block it to prevent it from propagating,” Han added.
To test out their findings, researchers attached a chemical tag to the hotspot and found that the tau fibrils stopped growing. This revealed that the proteins have to neatly stack on top of each other to form the fibrils, and this process only works when the hotspot site of one protein sticks to the other.
“If you have a tiny mismatch in the alignment of the tau shapes that stack to the fibril end, the structure will eventually stop growing,” said Han.
The findings could help researchers better under the tau protein and eventually even create synthetic proteins in the lab which would then allow scientists to develop diagnostic tools and therapies to address them.