Inside The Neighborhood Of Alzheimer’s Disease Proteins

A previously unrecognized form of chemical bonding could explain why amyloid beta proteins clump up to cause Alzheimer’s disease.

AsianScientist (Aug. 15, 2019) – Weak but numerous chemical interactions called through-space bonds could explain the abnormal protein structures that cause Alzheimer’s disease. These findings have been published in Scientific Reports.

In the traditional understanding of chemical bonding, atoms in large molecules must be side by side to share electrons. However, chemists at the University of Tokyo, Japan, have now shown that some atoms too far apart to bond are still in each other’s ‘electron neighborhoods.’

“This is so strange. It’s outside the common sense of organic chemistry,” said study leader Professor Tomohiko Ohwada.

Naming this interaction through-space bond path interactions, the researchers said that while individual interactions are extremely weak, they are common enough to add up to a potentially significant influence on the overall structure of large molecules. The researchers then tested the effect of through-space bond path interactions on the water-repelling portions of synthetically built mini amyloid beta sheets.

“We studied the amyloid beta structure because everyone knows it can cause disease, but nobody really knows how the problematic structure develops,” said Ohwada.

They found that through-space bond path interactions within and between the protein chains likely stabilize the structure and may help it clump together into disease-causing plaques.

Recognizing the location and nature of through-space bond path interactions may help researchers predict the true structure and behavior of a molecule based only on its chemical sequence. The team plans to expand their computations to the water-attracting portions of amyloid beta and to larger molecules.

“In theory, it might be possible to build an artificial molecule that could form through-space bond path interactions with natural proteins and change their activity,” said Ohwada.

The article can be found at: Zhai et al. (2019) Uncovering the Networks of Topological Neighborhoods in β-Strand and Amyloid β-Sheet Structures.


Source: University of Tokyo; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Asian Scientist Magazine is an award-winning science and technology magazine that highlights R&D news stories from Asia to a global audience. The magazine is published by Singapore-headquartered Wildtype Media Group.

Related Stories from Asian Scientist