7.Researchers one step closer to cracking Alzheimer’s puzzle
Research groups at TIFR, Mumbai, IISc, Bangalore and the University of Toronto working together, may have gotten the closest yet to figuring out how the toxic form of the Alzheimer’s molecule looks. This brings with it implications of development of better drugs to treat patients.
Alzheimer’s disease is a progressive form of dementia that is characterised by loss of short-term memory, deterioration in behaviour and intellectual performance, besides slowness of thought. It may occur in middle age or in old age, and while a lot of research is on for drug treatments, none has been successful.
While it is widely accepted that a specific form of the Amyloid beta molecule is a major player in causing Alzheimer’s, the shape and form of this remained elusive, experts say.
The excitement now is that scientists have caught a glimpse of the molecule during its attempt to enter a cell membrane, using a new method involving laser light and fat-coated silver nanoparticles.
“It is a rare protein and is difficult to probe. It was slightly fortuitous that we found it, using a modified version of Raman Spectroscopy. Usually the signal from this is weak, but we mimicked the cell’s outer layer by encasing silver nanoparticles in a fat membrane,” says Sudipta Maiti, of TIFR, who co-directed the research with P.K. Madhu. The Amyloid beta molecules were fooled into piercing this ‘membrane’ and the nanoparticles enhanced the signals, allowing scientists to see it at that point.
When proteins aggregate, or gang up to form a structure, they shift shapes. “At some stage of ganging up they suddenly start attacking the cell membrane and that’s where toxicity begins. How they enter the membrane, and what they look like when entering the membrane is key,” he says.
Amyloid beta molecules
The ‘lock’ looks like a bunch of Amyloid beta molecules each in the shape of a hairpin, but with a twist, TIFR has said in a release. Debanjan Bhowmik, the lead contributor of the study, says “This has been suspected earlier, but what we found was an unexpected twist in the structure, now becoming a beta-hairpin — very different from the typical hairpin structure people imagined.” This technique might also help in finding the shape of similar proteins in future, Dr. Maiti adds.
The findings were published in the journal ACS Nano this week.
If indeed it turns out to be the ‘lock’ for Alzheimer’s then the discovery will facilitate new efforts to finding a key — an intelligent drug candidate designed to attack the lock. “We have been working on the project for nearly 12 years now, and it is only now that we have started working with a few colleagues from the Institute of Chemical Technology who have the expertise in the field of intelligent design of drug molecules,” Dr. Maiti says.
“The use of technology to identify peptides and peptide transformations, which helps us understand the structure in great detail, is important — both for definitive diagnosis and definitive treatments. Once defined, researchers could adopt the technique to study wider samples, and this will lead to a greater understanding and modification of processes, eventually to better clinical care,” says Ennapadam S. Krishnamoorthy, Chennai-based senior neuropsychiatrist, and founder, Neurokrish.