Authors: Alice Weatherston
A joint team of researchers from the Tata Institute of Fundamental Research (TIFR; Mumbai, India), the Indian Institute of Science (Bengaluru, India) and the University of Toronto (ON, Canada) may have uncovered the molecular structure of the elusive toxic form of amyloid beta. If correct, the findings could aid in the design of effective drugs for targeting the amyloid beta pathway to Alzheimer’s.
“Everybody wants to make the key to solve Alzheimer’s disease, but we don’t know what the lock looks like. We now have a glimpse of something which could be the lock. Maybe it’s still not the real thing, but as of now, this is our best bet,” explained Sudipta Maiti (TIFR).
The research team studied the amyloid beta molecule during its attempt to attack the outer covering of a cell decoy by using a modified version of Raman Spectroscopy, involving laser light and fat-coated silver nanoparticles, which mimicked the outer membranes of living cells. The modification to the technique allowed greater resolution of the laser-induced signals from the amyloid beta, enabling minor signals that would previously have been unnoticed to be revealed.
Gilbert Walker (University of Toronto) discussed the use of the fat-coated silver nanoparticles: “While the amyloid beta got fooled by it and stuck to the membrane, the silver inside enhanced the signal to a measurable level and acted as a light beacon to reveal the peptide signature.”
The signals revealed a bunch of amyloid beta molecules arranged in a hairpin shape as previously suspected, however there was also an unexpected twist in the structure, creating a beta-hairpin as opposed to the typical hairpin structure predicted. “This may allow these bunch of amyloid beta molecules to form toxic pores in the cell membranes,” explained Debanjan Bhowmik (TIFR).
Whilst the findings of the study shed light on a previously unknown aspect of Alzheimer’s disease and could ultimately aid in the development of new therapies, the team believe that the modified technique also provides an opportunity for deciphering the structures of a whole breadth of membrane molecules from different diseases that are also as yet unknown.
Source: Tata Institute of Fundamental Research press release via Eurekalert http://www.eurekalert.org/pub_releases/2015-08/tiof-gfs082515.php ; Bhowmik D, Mote KR, MacLaughlin CM et al. Cell-membrane-mimicking lipid-coated nanoparticles confer raman enhancement to membrane proteins and reveal membrane-attached amyloid-β conformation. ACS Nano. (2015) DOI: 10.1021/acsnano.5b03175